Expression of oestrogen receptor-beta in apocrine carcinomas of the breast.

AIMS: Apocrine carcinoma of the breast seldom expresses oestrogen receptors (ER) or progesterone receptors (PR), but frequently expresses androgen receptors (AR). Because of this unusual hormone receptor status, it has been suggested that oestrogens have a less important role in the pathogenesis of apocrine carcinoma. The ER status of apocrine carcinoma has been studied for one kind of ER, the classic receptor now named ER-alpha; however, the status of ER-beta, a secondary oestrogen receptor, has not been examined systematically in apocrine carcinoma. The aim was to study ER-beta status in apocrine carcinoma. METHODS AND RESULTS: The expression of ER-beta was examined immunohistochemically in 48 apocrine carcinomas and compared with clinicopathological factors and ER-alpha, PR and AR status. ER-beta positivity was observed in 35 cases (73%), regardless of any clinicopathological factors or the status of other receptors. The results of ER-beta mRNA analysis supported the immunohistochemical results. CONCLUSIONS: The significance of oestrogens in apocrine carcinoma should not be dismissed at present when the role of ER-beta remains to be determined. Studying the action of oestrogen or antioestrogen in apocrine carcinoma may reveal a role for ER-beta independent of ER-alpha and raise the potential of hormonal therapy for these tumours.

CIH-Tokyo experience with breast-conserving surgery without radiotherapy: 6.5 year follow-up results of 1462 patients.

When breast-conserving therapy was introduced at the Cancer Institute Hospital (CIH) in Tokyo in 1986, we instituted our own strategy as follows: 1) every effort is to be made for complete tumor resection while avoiding deformity of the breast, and 2) radiotherapy (RT) is applied only to the patients with positive surgical margins. This is, in turn, to clarify the group of patients in whom postoperative RT can be safely spared. Among 9670 patients operated on for primary breast cancer during the 16.5 year period from 1986 to 2002 at CIH, there were 2449 patients who underwent breast-conserving surgery (BCS). During the 6.5 years mean follow-up period, ipsilateral intrabreast tumor recurrence (IBTR) developed in 99 of the 2449 patients, with an overall rate of 4.0% and an annual rate of 0.62%. These 2449 patients were categorized into four subgroups according to either negative or positive margins and with or without radiotherapy. The IBTR rates and the number of patients in each subgroup were 5.5% in 1351 margin(-)RT(-) patients, 1.0% in 307 margin(-)RT(+) patients, 2.4% in 680 margin(+)RT(+) patients, and 4.5% in 111 margin(+)RT(-) patients. These results either with or without RT seem to be quite comparable to or even better than the results of BCS with RT reported from Western countries, where less emphasis seems to be placed on completeness of the local tumor resection with BCS, while RT is administered to basically all patients following BCS. IBTR was categorized into true recurrence (TR) and second primary lesion (SP) according to the margin status at the time of BCS, the former being lesions developed in patients with positive margins and the latter being those in patients with negative margins. It was demonstrated that in patients with positive margins, TR was much more common than SP, whereas in patients with negative margins, these incidences were just the opposite (i.e., TR was 60% less common than SP) and postoperative RT was effective in preventing both TR and SP, the effect on the latter being much more striking. With RT, the incidence of developing TR in patients who had positive margins was reduced to almost equal to that in margin(-) patients treated with no RT. Our method of IBTR categorization is based on biological consideration and detailed histopathologic examination, and appears to be the only biologically reasonable means so far that has been proposed for distinction between these two biologically different entities. TR and SP can be further reduced to exceptionally low levels in patients who received RT despite negative margins, though it would not seem reasonable to administer RT to all of these patients because the actual number of patients who would benefit is comparatively small. From these observations, it seems that our imaging, pathologic examination, and surgical approaches for patients who are candidates for BCS have been highly valid, and our criteria for sparing postoperative RT as well as categorization of IBTR into TR and SP are quite appropriate. Although our results with BCS seem to deserve wide recognition, they are not from randomized clinical trials, so the findings must be confirmed by a study in order to investigate whether the results at CIH can be applied generally at other institutions.

Experience with intradermal injection and intradermal-plus-deep injection in the radioguided sentinel node biopsy of early breast cancer patients.

AIMS: Methods of administering (99m)Tc-phytate during sentinel node biopsy of early breast cancer patients were compared to improve the sensitivity of the technique. METHODS: Two injection methods, intradermal vs. intradermal-plus-deep injection, were compared in 648 early breast cancer patients. Intradermal injection was done in 323 consecutive patients (325 breasts), and intradermal-plus-deep injection was done in 325 consecutive patients (329 breasts). The following items were compared: (1) The number of axillary nodes detected scintigraphically and removed surgically, and the breast number of micrometastasis to axillary nodes; (2) The number of internal mammary nodes detected scintigraphically and removed surgically; and (3) The sensitivity of axillary SNB. RESULTS: The number of axillary nodes scintigraphically detected was 1.63+/-0.80 (mean+/-SD) in patients given intradermal injection, and was 1.82+/-0.94 in patients given intradermal-plus-deep injection. The number of axillary nodes surgically removed was 1.78+/-0.93 in patients given intradermal injection, and was 1.95+/-0.99 in patients given intradermal-plus-deep injection. The visualization of internal mammary nodes was superior with intradermal-plus-deep injection (5/325 for intradermal, and 51/329 for intradermal-plus-deep). The putative sensitivity was 71/72 (98.6%) for the intradermal-plus-deep method and 56/62 (90.3%) for the intradermal method. The frequency of detection of micrometastasis was 24 in 71 true positive (38.8%) for the intradermal-plus-deep method and 13 in 56 true positive (23.2%) for the intradermal method. CONCLUSIONS: The SNB procedure with the intradermal-plus-deep injection method detected more axillary and internal mammary nodes, more (not statistically significant) micrometastasis and improved the putative sensitivity more than the SNB procedure with the intradermal injection method.

Radioactivity thresholds for sentinel node biopsy in breast cancer.

AIMS: The aim of the present study is to clarify the level of radioactive lymph node should be biopsied after the most radioactive SN is removed. METHODS: SNB using radionuclide was performed in our hospital for 1179 primary breast cancers between April 2000 and October 2005; most (1177/1179) were performed successfully. Our criterion for harvesting SNs is to remove tissue until no radioactive site is present. The level of radioactivity and the order of removal of each lymph node were compared with pathologic results. RESULTS: More than 2 (overall average 1.9) radioactive SNs were biopsied in 686 of 1177 breasts. Cancer positive results were recorded for 142 breasts with multiple SNs. In 142 breasts, 64 showed metastasis to the most radioactive node only, 39 showed metastasis other than the most radioactive node only, and 39 showed the most radioactive node and other radioactive nodes. Moreover, if several other criteria were applied, false-positive cases were increased significantly. CONCLUSIONS: It is necessary to harvest radioactive lymph nodes other than the most radioactive. Moreover, efforts to remove every radioactive lymph node will minimize false-negative results.

Expression of GCDFP-15 and AR decreases in larger or node-positive apocrine carcinomas of the breast.

AIMS: Apocrine carcinoma of the breast is typically, though not always, positive for gross cystic disease fluid protein-15 (GCDFP-15). In order to clarify the clinical significance of GCDFP-15 in apocrine carcinomas, GCDFP-15 expression was examined in apocrine carcinomas of different stages and compared with clinicopathological factors. Apocrine lesions reportedly exhibit an unusual immunohistochemical status, expressing androgen receptors (AR) instead of oestrogen receptors (ER), progesterone receptors (PR), or bcl-2. Their expression was also examined. METHODS AND RESULTS: Fifty-two apocrine carcinomas were examined immunohistochemically. Thirty-nine (75%) and 29 (56%) were positive for GCDFP-15 and AR, respectively. GCDFP-15 positivity was significantly lower in infiltrating carcinomas than intraductal carcinomas (P = 0.0111). In infiltrating carcinomas, GCDFP-15 positivity was significantly low in tumours > or = 15 mm (P = 0.0005) and node-positive tumours (P = 0.0004). Similar phenomena were observed for AR. Rare cases were positive for ER (3.8%), PR (5.8%), and bcl-2 (1.9%). CONCLUSIONS: GCDFP-15 positivity is transient and should not be considered a definitive marker of apocrine carcinomas. Cases which have apocrine features but lack GCDFP-15 expression should rather be considered as advanced apocrine carcinomas. ER/PR/bcl-2 negativity will sometimes be helpful to confirm the diagnosis of apocrine carcinoma, because it is more consistent than GCDFP-15/AR positivity.

The effect of an old surgical scar on sentinel node mapping in patients with breast cancer: a report of five cases.

AIMS: To study the significance of lymphatic drainage disruption due to a surgical scar in sentinel node mapping (SNM) in breast cancer patients. METHODS: We reviewed patients with stage I breast cancer who had undergone SNM and had an old surgical scar in the ipsilateral breast. RESULTS: Of 534 breast cancer patients who had undergone SNM, five patients had an old scar in the ipsilateral breast. Inter-pectoral nodes, internal nodes, intramammary nodes, and contralateral axillary nodes were identified as sentinel nodes in three cases. In the remaining two cases, no sentinel lymph nodes were identified. CONCLUSIONS: An old surgical scar in the breast may cause lymphatic drainage disruption, resulting in abnormal radioactive colloid uptake during SNM.

Comparison of two-year and five-year tamoxifen use in Japanese post-menopausal women.

AIM: Large multicenter, randomized trials have revealed the advantages of using tamoxifen for 5 years vs 2 years in breast cancer patients. The aim of this report is to confirm the optimal duration of tamoxifen administration in a study of Japanese breast cancer patients. METHODS: Japanese post-menopausal estrogen receptor-positive breast cancer patients treated with mastectomy were randomly assigned to either a 5-year or 2-year course of tamoxifen. The primary endpoint was disease-free survival, with secondary endpoints of overall survival and a reduction in the development of metachronous contra-lateral breast cancer. RESULTS: A total of 256 breast cancer patients were randomized to a 5-year or 2-year tamoxifen administration group. After a median follow-up time of 81 months, there were no significant differences seen in terms of disease-free or overall survival (p=0.65 and 0.56, respectively). Furthermore, the impact of the 5-year use of tamoxifen on the development of contra-lateral breast cancer did not reach statistical significance (p=0.0511). However, 5-year tamoxifen use was closely associated with gynaecological complications (p=0.0081). CONCLUSION: We could not show a beneficial effect of using tamoxifen for 5 years over 2 years in Japanese estrogen receptor-positive patients. This is likely due to the small number of patients enrolled in our study; however, racial disparity may influence this result. A reevaluation is necessary to study the advantages of the 5-year use of tamoxifen in the Japanese racial subgroup.

The potential for oral combination chemotherapy of 5'-deoxy-5-fluorouridine, a 5-FU prodrug, and cyclophosphamide for metastatic breast cancer.

Preclinical studies have demonstrated the synergistic anti-tumour activity of combination therapy with the oral cytostatics, 5'-deoxy-5-fluorouridine (5'-DFUR) and cyclophosphamide (CPA), in human breast cancer xenograft models. This study was performed to evaluate the efficacy and safety of this oral combination chemotherapy in the treatment of metastatic breast cancer. In all, 101 patients with metastatic breast cancer were enrolled in the study, and the data for 94 eligible patients of these were evaluated. The patients received twice daily oral combinations of 5'-DFUR (1200 mg/body/day) and CPA (100 mg/body/day) for 2 weeks, followed by a 1-week rest period. After a median of 19 treatment cycles (range 1-66 cycles), 16 patients (17.0%) had a complete response, and 40 patients (42.6%) had partial responses. The response rate was 59.6% (95% CI, 49.0-69.6%). The median time to progression and overall survival times were 11.7 and 40.3 months, respectively. The toxicity was mild and tolerable, and the related grade 3/4 clinical adverse effects consisted of haematological toxicity in 21 patients (22%) and nonhaematological toxicity in five patients (5%). These results suggest that the oral combination chemotherapy of 5'-DFUR and CPA has low toxicity and is a novel, very convenient and effective treatment for metastatic breast cancer.

Comparison between solitary and multiple skeletal metastatic lesions of breast cancer patients.

BACKGROUND: Breast cancer has been the subject of many recent studies because it is a significant cause of death in women. This study was performed to clarify whether solitary skeletal metastasis has clinical significance compared with multiple skeletal metastasis. PATIENTS AND METHODS: Seven hundred and three patients who developed metastatic bone lesions up to September 2002 after beginning treatment for breast cancer from 1988 to 1998 were included. The lesions were classified first as solitary or multiple based on bone scan results and then according to anatomical distribution. Next, solitary-to-multiple conversion was investigated in patients with solitary skeletal metastasis. Then factors related to solitary or multiple skeletal metastasis were analyzed. The prognosis of skeletal metastasis was compared between patients with solitary or multiple metastatic bone lesions. A Cox proportional hazards model was used to test whether solitary skeletal metastasis compared with multiple skeletal metastasis was an independent factor of survival. RESULTS: Two hundred and eighty-nine patients (41%) had solitary skeletal metastasis and 414 patients (59%) showed multiple skeletal metastasis. The sternum was a frequent site for solitary skeletal metastasis (98 of 289, 34%), while other skeletal sites were more frequent in patients with multiple metastatic bone lesions (P <0.001). Solitary sternal metastatic lesions remained solitary longer than solitary metastatic bone lesions to places other than the sternum (P <0.001), but did not lengthen patient survival times (P = 0.871). The factors related to solitary skeletal metastasis are TNM stage (tumor-node-metastasis) and histology. The patients with earlier stage and favorable histology tend to have solitary skeletal metastasis. The patients with solitary skeletal metastasis lived longer than those with multiple metastatic bone lesions (P <0.001). Multivariate analysis revealed that a solitary metastatic bone lesion (P = 0.002) is an independent favorable prognostic factor in patients with skeletal metastasis. CONCLUSIONS: Solitary skeletal metastasis has a different anatomical distribution and is an independent prognostic factor in patients with skeletal metastasis.

Sentinel node detection using 99mTc-rhenium sulphide colloid in breast cancer patients: evaluation of 1 day and 2 day protocols, and a dose-finding study.

Sentinel node (SN) biopsy is a promising replacement for standard axillary lymph node dissection for the staging of early breast cancer, and various techniques have been studied to identify SNs with dye or radioactive colloid. This study assesses the effect of the dose of radioactivity and the time before biopsy in order to set standards for the use of 99mTc-rhenium sulphide for the detection of SNs in breast cancer patients. Sixty patients with stage T1-2 N0 M0 breast cancer underwent SN biopsy, which was immediately followed by standard axillary dissection to confirm the SN results. For SN biopsy, 99mTc-rhenium colloid was injected peritumorally. A 1 day (morning injection and afternoon surgery) or 2 day (day before afternoon injection and morning surgery) protocol was applied. A dose-finding study was performed simultaneously using 7.4-37 MBq for the 1 day protocol and 37-74 MBq for the 2 day protocol. A scintigram was taken at 2 h for the 1 day protocol and 16 h for the 2 day protocol. After the injection of blue dye, SN biopsy was performed with a gamma probe, followed by standard axillary node dissection. The radiation exposure received by the surgical team during the operation was monitored. Histopathological comparison between SNs and axillary nodes was performed. Patient characteristics that might affect the radiocolloid uptake by SNs were assessed. SNs were identified in all patients regardless of the dose or administration protocol used. Two patients showed false negative pathological SN results, and the negative predictive value was 96% and the positive predictive value was 100%. In addition, radiation exposure to the surgical team and the amount of radioactive surgical waste were low, especially at lower doses. Two groups of patient characteristics were related to SN uptake. One was the body mass index (BMI) and the other was the age or menopausal status. Patients with a larger BMI tended to take up a smaller amount of 99mTc colloid. Older or post-menopausal patients showed lower SN uptake. 99mTc-rhenium sulphide colloid is an efficient radiopharmaceutical for SN detection. Both 1 day and 2 day protocols have equally good efficacy, and the recommended dose is 7.4 MBq for the 1 day protocol and 37 MBq for the 2 day protocol. Patients with larger BMI and older or post-menopausal patients tend to take up less 99mTc colloid.

Breast conserving treatment without radiotherapy.

Radiotherapy (RT) is not always necessary for the prevention of ipsilateral breast recurrence in cases where cancer is not detected in the remaining breast tissue after breast conserving surgery. In addition, under these circumstances, the rate of a second primary cancer of the remaining breast is theoretically equal to the rate of contralateral breast cancer. In performing breast conserving treatment (BCT) at our institution we do not treat with RT if a strict serial pathological examination of the specimen (every 5 mm) reveals that the case has been safely resected (negative surgical margins). From 1986 to 1998, 827 patients (157 were ductal carcinoma in situ, and 670 were invasive) underwent BCT without RT at the Cancer Institute Hospital. Ipsilateral breast cancer was observed in 46 cases or 5.6% (0.85% annually) during a median observation period of 67 months. Of these 46 cases, 19 (2.3%) were diagnosed as a recurrence and 27 cases (3.3%) were second primary cancers. This recurrence rate is equivalent to the rate observed in 406 cases of BCT (1.7%) that were treated with RT. Most of these cases had shown positive surgical margins. Furthermore, the rate of occurrence of second cancers is not significantly different from the rate of occurrence of contralateral breast cancers. These results suggest that, by selecting irradiation cases based on careful pathological examinations, BCT can be safely performed.

Overrepresentation of the EBAG9 gene at 8q23 associated with early-stage breast cancers.

EBAG9, an estrogen-responsive gene located at 8q23 was identified in an effort to clone CpG-binding sites. Its product was later found to be identical to RCAS1, a cancer cell-surface antigen implicated in immune escape. We determined the sequence of the complete cDNA and the genomic structure for EBAG9. EBAG9 gene copy number in 21% (27 of 129) primary breast cancers we examined; EBAG9 mRNA was consistently expressed in cancer cell lines. Detailed physical mapping of the 8q arm, including polymorphic markers for EBAG9 and the CMYC loci, revealed allelic gain of either EBAG9, CMYC, or both, in 45% (58 of 129) of the breast cancers we examined. The EBAG9 gene was increased exclusively in 16 of the 27 tumors showing gain at that locus; the other 11 showed gain of a larger chromosomal region containing both EBAG9 and CMYC. Analysis of subsequent series of 144 primary breast cancers for allelic gain at EBAG9 and CMYC locus showed a similar degree of gain at EBAG9, CMYC, or both. When a total of 273 breast cancers from two series were combined and analyzed for clinicopathological correlation, almost all of the tumors with EBAG9 increased but not those with CMYC. Twenty-eight of 29 were T1/T2 stage carcinomas (<5 cm in diameter), whereas one third (21 of 61) of the tumors in which CMYC was increased but EBAG9 was not, were advanced T3-stage tumors (P = 0.0012). These data suggest that EBAG9 and CMYC gene are independent targets of gain and that overrepresentation of EBAG9 may play a specific role in early stages of breast carcinogenesis.

Allelic losses as prognostic markers for breast cancers.

Specific allelic losses in the DNA of tumor cells are potential indicators of postoperative prognosis. Patients whose tumors showed allelic losses at 1p34, 3p25, 8p22, 13q12, 17p13.3, or 17q21.1 had a significantly higher risk of postoperative mortality than women whose tumors retained both alleles at those loci (the 5-year mortality rates in patients with loss vs those with retention were: at 1p34, 23% vs 10%, P = 0.0100; at 3p25, 22% vs 9%, P = 0.0014; at 8p22, 24% vs 7%, P = 0.0177; at 13q12, 19% vs 8%, P = 0.0093; at 17p13.3, 19% vs 9%, P = 0.0078; and at 17q21.1, 17% vs 10%, P = 0.0475). Allelic losses at these loci may serve as negative prognostic indicators to guide postoperative management, especially in the selection of patients who should be offered intensive adjuvant therapy.

Association of allelic losses at 3p25.1, 13q12, or 17p13.3 with poor prognosis in breast cancers with lymph node metastasis.

To identify specific allelic losses that might correlate with postoperative mortality of patients with node-positive breast carcinomas, we examined tumors from a cohort of 263 such patients, who were followed clinically for 5 years postoperatively, for allelic losses among 18 microsatellite markers. Patients whose tumors had lost an allele at 3p25.1, 13q12, or 17p13.3 had significantly higher risks of mortality than those whose tumors retained both alleles at those loci. At 3p25.1, the 5-year mortality rate was 33.8% among patients with losses vs. 16.8% with retention (P = 0.0154); at 13q12, 30.3% vs. 13.0% (P = 0.0241); and at 17p13.3, 30.4% vs. 16.2% (P = 0.0243). Combined losses at 3p25.1 and 17p13.3 increased the predicted postoperative mortality risk by a factor of 4.9 (5-year mortality rate of 38.2% vs. 8.0%, P = 0.0006), and combined losses at 3p25.1 and 13q12 raised the predicted postoperative mortality risks by a factor of 2.9 (34.7% vs. 12.7%, P = 0.0441). These data indicate that loss of heterozygosity (LOH) at any one or a pair of loci at 3p25.1, 13q12, or 17p13.3 is a significant predictor of postoperative mortality for breast-cancer patients.

What do breast cancer patients benefit from staging bone scintigraphy?

BACKGROUND: A review and analysis of breast cancer treatment records were conducted to establish criteria for performing disease staging by bone scintigraphy in Japanese breast cancer patients. METHODS: Records from 5538 consecutive Japanese breast cancer patients from January 1988 to December 1998 were reviewed and analyzed to determine bone metastasis status at the time of initial treatment. Correlation between metastasis to bone and factors known before and after surgery was analyzed using logistic regression. RESULTS: The overall incidence of metastasis to bone was 2.13% [95% confidence interval (CI): 1.77-2.55%, 118/5538]. Multivariate logistic analysis revealed that tumor size, nodal involvement and histopathology correlated with metastasis to bone. Patients with tumors larger than 30 mm had a significantly higher probability of metastasis to bone, as did patients with lymph node evaluation results N > or = 1. The incidence of metastasis to bone was 0% in patients with stage 0 disease, 0.08% in stage I patients, 1.09% in stage II patients, 9.96% in stage III patients and 34.04% in stage IV patients. Stage II patients were sub-classified by tumor size T (small, 21-30 mm; and large, 31-50 mm), nodal involvement N and histopathology. The incidence of metastasis to bone in stage II patients was higher in patients with large tumors, scirrhous carcinoma or invasive lobular carcinoma or both. CONCLUSION: Bone metastasis correlated with tumor size (T), lymph node involvement (N) and histopathology. Using the criteria that bone scintigraphy is not necessary in populations with a < 1% incidence of bone metastasis, but is recommended at incidence > 3%, the following conclusions were drawn. Staging by bone scintigraphy provided no benefit to patients whose disease was stage I or less, stage II with small tumors or stage II with large tumors marked by low-grade histopathology (papillotubular cancer). Bone scintigraphy is recommended in patients whose disease is stage II with large tumors marked by high-grade histopathology (scirrhous or invasive lobular cancer), stage III or stage IV. Consequently, staging by bone scintigraphy could be avoided in 71% (3943/5538) of Japanese breast cancer patients.

Allelic losses of loci at 3p25.1, 8p22, 13q12, 17p13.3, and 22q13 correlate with postoperative recurrence in breast cancer.

We previously defined 18 chromosomal regions in which frequent allelic losses were observed in breast cancers (T. Sato et al., Cancer RES:, 50: 7184-7189, 1990; Y. Harada et al., Cancer (PHILA:), 74: 2281-2286, 1994; I. Ito et al., BR: J. Cancer, 71: 438-441, 1995; K. Tsukamoto et al., Cancer (PHILA:), 78: 1929-1934, 1996; S. Matsumoto et al., Genes Chromosomes Cancer, 20: 268-274, 1997; T. Yokota et al., JPN: J. Cancer RES:, 88: 959-964, 1997; K. Tsukamoto et al., Cancer (PHILA:), 82: 317-322, 1998; A. Iida et al., Genes Chromosomes Cancer, 21: 108-112, 1998; K. Fukino et al., Genes Chromosomes Cancer, 24: 345-350, 1999; T. Yokota et al., Cancer (PHILA:), 85: 447-452, 1999; Y. Utada et al., JPN: J. Cancer RES:, 91: 293-300, 2000). To identify specific allelic losses that might correlate with postoperative recurrence, we examined tumors from a cohort of 504 breast cancer patients, who were followed clinically for 5 years postoperatively, for allelic losses of 18 microsatellite markers. Patients whose tumors had lost an allele at 3p25.1, 8p22, 13q12, 17p13.3, or 22q13 had significantly higher risks of recurrence than those whose tumors retained both alleles at those loci; at 3p25.1, the 5-year recurrence rate was 27% among patients with losses versus 18% with retention (P = 0.0131); at 8p22, 27% versus 14% (P = 0.0129); at 13q12, 28% versus 15% (P = 0.0109); at 17p13.3, 27% versus 20% (P = 0.0482); and at 22q13, 29% versus 20% (P = 0.0477). These data indicate that loss of heterozygosity at any one of these five specific loci is a significant predictor of postoperative recurrence among patients who have undergone surgery for breast cancer. These allelic losses can serve as negative prognostic indicators to guide postoperative management of patients.

Is the UICC pathological node status system useful? Comparison with the Japanese Breast Cancer Society pathological node status system.

BACKGROUND AND OBJECTIVES: The UICC and the Japanese Breast Cancer Society have different TNM classifications. There is a large discrepancy between the pathological node status in the UICC (UICC-NS) and JBCS (JBCS-NS) systems. We compared the UICC-NS with the JBCS-NS. METHODS: Reviewed were data on 1,684 invasive ductal carcinomas at the Cancer Institute Hospital from 1981 to 1986. Each case was categorized according to the UICC-NS and JBCS-NS, respectively. Overall survival 10 years after surgery (OS) by UICC-NS and JBCS-NS was calculated by the Kaplan-Meier method. RESULTS: OS with UICC-NS and number of case were, respectively, 87.8% and 968 for pN0, 83.9% and 93 for pN1a, 71.6% and 190 for pN1bi, 60.0% and 25 for pN2, 58.8% and 51 for pN1bii, 55.7% and 238 for pN1biii, 54.2% and 24 for pN1biv, 44.8% and 58 for pN3, and 20.6% and 34 for pM (LYM). Differences between pN1a and pN1bi and pN3 and pM (LYM) were significant (p < 0.05). In JBCS-NS, they were 87.8% and 968 for n0, 75.3% and 384 for n1 alpha, 51.3% and 152 for n1 beta, 46.6% and 141 for n2, 21.2% and 33 for n3, 0% and 2 for n4d and n4i, respectively. Differences between n0 and n1 alpha, n1 alpha and n1 beta, and n2 and n3 were significant (p < 0.05). CONCLUSIONS: With a large number of classification factors, UICC-NS was more complicated and hard to show significant difference in OS than JBCS-NS. But the latter also had redundant classifications. So, it is necessary to establish a new, simple, and easy-to-register node classification in future.

[Sentinel node detection of patients with breast cancer by radionuclide method: consideration of radiation safety].

Sentinel node was detected by 99mTc labeled nanocolloid in five patients with breast cancer. Surgery of breast cancer was done at 16 hours after the administration of 74 MBq of 99mTc labeled nanocolloid. Sentinel node was searched by scintigraphy prior to surgery and by gamma-probe during surgery. Radioactivity of injected site, sentinel nodes, blood contaminated gauze, and other garbage was measured by GM detector. Radiation to medical staffs was monitored by a pocket radiation detector and film batches. Sentinel nodes were successfully detected both by scintigraphy and gamma-detector. More than 70% of radioactivity remained in the administered site at 16 hours. Small amount of radioactivity was detectable in the sentinel node. Almost no radioactivity was detectable in blood-contaminated gauze and other garbage. Radiation dose to the main surgeon was 4 to 6 microSv per surgery by a pocket radiation detector. Radiation dose to the assistant surgeon was 2 microSv per surgery. Radiation dose by labeling or injection was 0 to 1 microSv per procedure. No detectable radiation was measured by film batches. It is concluded that the detection of sentinel node by 99mTc labeled nanocolloid is a safe procedure from the point of radiation safety consideration.

Absence of endothelial cells, central necrosis, and fibrosis are associated with aggressive inflammatory breast cancer.

We recently established a new human inflammatory breast cancer (IBC) xenograft (WIBC-9) originating from a patient with IBC. The graft was transplantable in BALB/c nude and severe combined immunodeficient (SCID) mice. WIBC-9 was frequently accompanied by lung metastasis and exhibited erythema of the overlying skin, reflecting its human counterpart. Histological study of the original tumor and WIBC-9 revealed invasive ductal carcinoma with a hypervascular structure of solid nests and marked lymphatic permeation in the overlying dermis. In the central part of the solid nests, absence of endothelial cells, central necrosis, and fibrosis were observed. In vitro, WIBC-9 formed tube-like structures and loops, reflecting its in vivo feature and its human counterpart. WIBC-9 exhibited aneuploidy, ErbB-2 gene amplification, and an absence of estrogen receptor and progesterone receptor, which is consistent with IBC. Comparative studies of WIBC-9, three established non-IBC xenografts, and a human breast cancer cell line (SK-BR3) by reverse transcription-PCR, ELISA, and immunohistochemistry indicated that certain human genes (interleukin 8, vascular epidermal growth factor, basic fibroblast growth factor, angiopoietin 13, Flt-1, Tie-2, and Tie-1) and certain murine genes (integrin alpha(v)beta3, flt-1, tie-2, vascular epidermal growth factor, and CD31) were overexpressed in exposure to tumor cells. The molecular basis and these unique histological features may be associated with aggressive IBC on angiogenic and nonangiogenic pathways.

[Day surgery for breast cancer].

In Japan, day surgery for breast cancer usually means partial mastectomy without axillary dissection for small carcinoma under local anesthesia in the outpatient clinic. If histopathological examination of the specimens by serial section reveals that the cancer is noninvasive and completely resected with negative surgical margins, no additional surgery under general anesthesia is needed, and the patient does not require hospitalization. We call this procedure "probe lumpectomy". From 1991 to 1998, 169 patients underwent probe lumpectomy in our institution, and there were no major complications. Of these 169 patients, 64 did not require hospitalization. Ipsilateral breast cancer was observed in two patients, and these tumors were diagnosed not as recurrence but as second primary cancers. No distant metastases were observed. As sentinel node biopsy, which is not always easy under local anesthesia, becomes more common, the indications for day surgery or short-stay surgery will expand. As breast cancer is a malignant disease, informed consent and careful follow-up are needed if the treatment is completed only in the outpatient clinic.