The Clinical Significance of Hormonal Receptors in Breast Cancer

PURPOSE: Clinically, the detection of steroid hormone receptors, estrogen receptor (ER) and proges terone receptor (PR), has been used not only as a prognostic marker but also as a predictor of hormone response in breast-cancer patients. We performed this study to evaluate the clinical significance of hormone receptors in breast cancers in Korea. METHODS: We have collected data about hormonal receptors from breast-cancer patients of Kangnam St. Mary's Hospital, The Catholic University of Korea, since 1984. A total of 544 patients were followed up and their clinicopathological results were analyzed retrospectively by using medical records. The survival analysis was performed by using the Kaplan-Meier method. RESULTS: The mean age of the patients was 47.3 years, and the peak of age distribution was noted in the 5th decade. The premenopausal patients were 358 (65.8%), and the postmenopausal patients were 186 (34.2%). The median follow-up period was 4.5 years. The results of ER/PR status were as follows: (+)/(+) in 191 patients (35.1%), (+)/(-) in 82 patients (15.1%), (-)/(+) in 74 patients (13.6%), and (-)/(-) in 197 patients (36.2%). The positive rates of ER and PR were 52% or 55% in premenopausal patients and 46% and 36% in postmenopausal patients, respectively. In the univariate analysis of the overall survival by the Log-rank test, the significant variables were stage (p=0.0004), node metastasis (p=0.0000), lymphatic invasion (p=0.0000), vein invasion (p=0.0558), ER (p=0.0397), PR (p=0.0538), adjuvant hormone therapy (p=0.0010), the duration of hormone therapy (p=0.0004). In the multivariate analysis of the overall survival by using the Cox regression test, the significant variables were ER (p=0.0070), adjuvant hormone therapy (p=0.0234), adjuvant chemotherapy (p=0.0493) and mean ingful results were noted in the duration of hormonal therapy (p=0.0629), lymphatic invasion (p=0.0752) and tumor size (p=0.1726). CONCLUSION: The results of this study suggest that the pattern of hormonal receptor status according to menopause status might be different from that of western patients and confirmed hormonal receptors as prognostic markers and predictors of hormone therapy in breast cancer.

Chest Well Muscle Changes after A Mestectomy Findings of Chest CT / 한국유방암학회지

BACKGROUND: Chest CT after a mastectomy in breast cancer patients is usually performed to detect recurrence or metastasis. It is essential for surgeons an radiologists to know the appearance of the chest wall in a postmastectomy state. Especially, muscle atrophies of the chest wall, such as that of the pectoralis major muscle, indicate whether the modified radical mastectomy (MRM) was properly performed or not. MATERIALS AND METHODS: We performed a retrospective analysis of chest wall changes in mastectomy patients with follow-up chest CT finding to evaluate the results of MRMs. The medical records and CT findings of chest wall atrophy for a total of 38 patients who were treated at Kangnam St. Mary's Hospital, the Catholic University of Korea, were reviewed. The mean age was 58.3 years, and the interval between operation and follow-up CT was 6.6 years. The operations performed were a radical mastectomy (RM) in 3 patients and a MRM in 35 patients: Petey in 28 patients, Auchincloss in 6 patients, and Scanlon in 1 patient. RESULTS: In the RM, muscle atrophies were noted at the m, subscapularis in 3 patients (100%), the m. serratus anterior in 2 patients (66.7%), and the m. lattisimus dorsi in 1 patient (33.3%). In MRM, the Patey and Auchincloss operations showed m. pectoralis major atrophies in 22 patients (78.8%) and 5 patients (83.3%) respectively. Additionally m. pectoralis minor atrophy was noted in all 6 patients (100%) who underwent the Auchincloss operation. However. there was no muscle atrophy in patients who received Scanlon operation. CONCLUSIONS: These results suggest that lateral pectoral nerve injury is the main cause of m. pectoralis major atrophy in a MRM. The Scanlon operation which preserves the serve by dividing the pectoralis minor m. at its origin is a suitable operation for chest-wall muscle preservation. We hope that by the future study, we can confirm the best way of preventing chest-wall muscle atrophy in MRMs.

The Expression of Thymidylate Synthase in Breast Cancer / 한국유방암학회지

Fluorouracil is well known as a standard chemotherapeutic drug in breast cancer and other cancers that is converted to flurodeoxyuridine monophosphate (FdUMP) and leads to the inhibition of thymidylate synthase (TS) in tumor tissue. The role of this enzyme is the catalysis of the methylation from deoxyuridine monophosphate (dUMP) to deozythymidine monophosphate (dUMP), which is a very important process for DNA synthesis in tumor tissues. Increased level of TS protein correlates inversely with sensitivity and response to 5 FU in human cancer cell lines. Authurs evaluated the TS expression level using the immunohistochmical staining and analysed their relationship with other prognostic factors and clinical outcome of breast cancer patients. The results were as follows; 1) TS level was not related histopathologic stage, involvement of axillary lymph nodes, estrogen receptor, progesterone receptor, recurrent type, primary tmor and recurrent tumors, disease free survival rate. 2) TS level was associated with e-erbB2 overexpression. 3) c-erbB2 overexpression was related with recurrence rate. 4) TS level appeared to be related with recurrence rate. So w conclude the TS level can be used as an independant prognostic predictor on breast cancer patients.

Telomerase Activity in Breast Cancer and Benign Breast Disease of Korea / 한국유방암학회지

BACKGROUND: Telomerase is an RNA-dependent DNA polymerase that compensates for the telomere shortening that occurs in its absence. Reactivation of telomerase is thought to be an important step in cellular immortalization, and recent studies have indicated that telomerase activity is often detected in primary human malignancies. The purpose of this study is to identify telomerase activity in breast cancer. MATERIALS & METHODS: Telomerase activities were analyzed in the samples of 12 breast cancer tissues and 11 benign breast disease tissues by TRAPeze ELISA detection kit (Oncor, Gaithersburg, USA). All samples were obtained from the excised mass at the time of specimen removal in the operating room and stored in liquid-nitrogen tank. RESULTS: Telomerase activity was detected in 10 of 12 (83.3%) breast cancer samples and 4 of 11 (36.4%) benign breast disease samples. The detection of telomerase activity in diagnosis of breast cancer has validity: 83.3% sensitivity rate, 63.6% specificity rate, 71.4% (+) predictability rate, 77.8% (-) predictability rate. The telomerase activity correlates with the estrogen receptor status (p=0.009). CONCLUSION: The telomerase activity can be detected in breast cancer sensitively. Further study with sufficient samples is needed to establish detection of telomerase activity as diagnostic tool in breast cancer.

Therapeutic Effects of Paclitaxel (Taxol ) in Metastatic Breast Cancer

BACKGROUND: Metastatic breast cancer is a systemic disease, and its treatment aims at the palliation or cure of the disease. In recent years, good results have been reported in the treatment of metastatic breast cancer by using single-agent paclitaxel chemotherapy. METHODS: We performed a retrospective study by analyzing the medical records of patients treated at Kangnam St. Mary's Hospital between May 1995 and May 1997. A total of 29 patients with metastatic breast cancer were treated by a 135-mg/m2, 3-hour infusion of paclitaxel. The results were reviewed with respect to the response rates and the toxicities of paclitaxel. RESULTS: The overall response rate was 13.8%: CR (complete response rate) 3.4% (1 out of 29) and PR (partial response rate) 10.3%(3 out of 29). The most common and severe toxicity was leukopenia. However, there was no mortality, and the patients were tolerated this therapy. CONCLUSIONS: Paclitaxel as a single-agent therapy for metastatic breast cancer is tolerable, but less effective, than reported.

Chest Wall Muscle Changes after a Mastectomy: Findings of Chest CT

BACKGROUND: Chest CT after a mastectomy in breast cancer patients is usually performed to detect recurrence or metastasis. It is essential for surgeons and radiologists to know the appearance of the chest wall in a postmastectomy state. Especially, muscle atrophies of the chest wall, such as that of the pectoralis major muscle, indicate whether modified radical mastectomy (MRM) was properly performed or not. METHODS: We performed a retrospective analysis of chest wall changes in mastectomy patients with follow-up chest CT findings to evaluate the results of MRMs. The medical records and CT findings of chest wall atrophy for a total 38 patients who were treated at Kangnam St. Mary's Hospital, the Catholic University of Korea, were reviewed. The mean age was 58.3 yeras, and the interval between operation and follow-up CT was 6.6 years. The operations performed were a radical mastectomy (RM) in 3 patients and a MRM in 35 patients: Patey in 28 patients, Auchincloss in 6 patients, and Scanlon in 1 patient. RESULTS: In the RM, muslce atrophies were noted at the m. subscapularis in 3 patients (100 %), the m. serratus anterior in 2 patients (66.7%) and the m. lattisimus dorsi in 1 patient (33.3%). In MRM, the Patey and Auchincloss operations showed m. pectoralis major atrophies in 22 patients (78.8%) and 5 patients (83.3%) respectively. Additionally m. pectoralis minor atrophy was noted in all 6 patients (100%) who underwent the Auchincloss operation. However, there was no muscle atrophy in patients who received scanlon operation. CONCLUSIONS: These results suggests that lateral pectoral nerve injury is the main cause of m. pectoralis major atrophy in MRM. The scanlon operation which preserves the nerve by dividing of pectoralis minor m. at its origin is a suitable operation for chest-wall muscle preservation. We hope that by the future study, we can confirm the best way of preventing chest-wall muscle atrophy in MRMs.

The Expression of c-erbB-2 and CD44 Gene in Breast Cancer / 한국유방암학회지

There are some controversial opinions on the prognostic value of metastasis-associated tumor markers in breast cancer. Out of them, the overexpression of c-erbB-2 proto-oncogene or CD44 gene has been debated on their activities in promoting metastatic potential. To determine the relationship between expression of both genes, and, clinicopathological parameters and disease outcomes including relapse and survival, 48 archival paraffin-embedded breast-cancer tissues were stained using monoclonal antibody against each gene product by immunohistochemical staining method, and the result was analyzed. The positive expression rates of c-erbB-2 and CD44 genes were 45.8% and 18.8%, respectively. The co-expression rates of both positives and both negatives were 14.6% and 50.0%, respectively. Except the statistically significant positive correlation between CD44 and tumor size (P=0.003), the expression rates of c-erbB-2 and CD44 had no significant relationship with tumor size, stge, lymph node status, and disease recurrence (p>0.05). In the positive expression cases for CD44, disease-free survival (DFS) and overall survival (OS) in months were shorter than the negative ones (53+/-8 vs. 64+/-5 and 67+/-8 vs. 77+/-5 S.E.) And, the c-erbB-2 positive cases had longer OS than the negative ones (78+/-6 vs. 71+/-6). The OS of positive co-expression cases with the c-erbB-2 and CD44 was shorter than that of one-gene expression ones (66+/-6 vs. 75+/-7). So the OS result observed in the expression of c-erbB-2 alone was reversed in the co-expression study. Though these results had no statistically significant level (p>0.05), we suggest a question that if there is any interaction or dependency between c-erbB-2 and CD44 expression in a view of disease process including OS. Finally, further randomized controlled studies are advisable for the reproducible and significant results.

The Effect of Tamoxifen of the Estrogen Receptor cDNA-Iipofected MDA-MB-231 Human Breast Cancer Cells / 한국유방암학회지

BACKGROUND: The loss of estrogen and progesterone receptors appears to be associated with a progression to less-differentiated and hormone-independent tumors. The gain of hormone independency over time even in estrogen receptor-positive tumors has become another obstacle to endocrine therapy for breast cancer. We tried to regain the hormone dependency in estrogen receptor-negative breast cancer cells by lipofecting estrogen receptor cDNA. MATERIALS AND METHODS: The mutant human estrogen receptor cDNA (pSG5-HE0) was lipofected into estrogen receptor-negative human breast cancer cell line MDA-MB-231, in an attempt to restore their sensitivity to antiestrogen. Then the effects if 17 beta -estradiol and tamoxifen were studied by counting viable cell numbers after treating the lipofected cell line with either one or together. RESULTS: The cell growth was most profoundly inhibited in 4 days after lipofection with mutant human estrogen receptor cDNA, which was overcome after that days. Tamoxifen, as an antiestrogen, showed a growth inhibitory effect slightly strong over combined conditions of tamoxifen and 17 beta estradiol compared to estrogen-treated group and to control. CONCLUSIONS: The temporary induction of estrogen receptor by lipofection with pSG5-HE0 on estrogen receptor-negative human breast cancer cell line MDA-MB-231 showed negative growth control on these cells by tamoxifen, indicating that liposome-mediated estrogen receptor transfection may be used as a novel therapeutic strategy for hormone independent human breast cancers in the near future.

Branchial Anomalies in Korea: A Survey by the Korean Association of Pediatric Surgeons

The survey on branchial anomalies was conducted by Korean Association of Pediatric Surgeons. A total of 173 cases were reported, which were managed by 36 members and cooperators during the three years from January 1, 1993 through December 31, 1995. The following results were obtained by retrospective analysis of the 173 cases of branchial anomalies. The presenting symptoms were cervical mass in 101 cases, pit with or without discharge in 71, cervical abscess in 47 and respiratory difficulty in 3. The average age of the patients with cervical abscess was 52 months. Seventy(79%) of 89 patients with branchial anomalies and a cystic mass had their first clinical manifestations by 1 year of age, while 40(51%) of 78 patients with only a branchial cyst had their first clinical manifestation in first year of life. Radiologic studies were carried out in 77 patients(43%). The preferred diagnostic modalities were ultrasonography(47 patients), simple neck radiogram(l9) and CT scan(17). Preoperative diagnosis was correctly made in 156(91%) of 173 patients. Seventeen patients were incorrectly diagnosed as thyroglossal duct cyst in 5 patients, cystic hygroma in 4, dermoid cyst in 3, and lymphadenopathy in 3. There were no remarkable difference in sex and laterality of presentation but bilateral lesions were found in 9(5%) patients and unusual locations of the anomalies were the manubrium, left subclavicular area, median cervial area, preauricular and parotid area. There were 78(45%) patients with cyst, 52(30%) patients with sinus, 35(20%) patients with fistula and 8(5%) patient with skin tag. Embryological classification was possible in only 64(37%) patients. The 2nd branchial anomaly was present in 50 (78%), the 1st branchial anomaly in 10(18%), and the 3rd or 4th branchial anomaly in 4(6%). Histopathological study of the lining epithelium(N=134) is recorded that 45% were lined with squamous epithelium, 17% with respiratory epithelium, 6% with. squamous and respiratory epithelium, 14% with inflammatory change. Lymphoid tissue was common(62%) in the wall of the lesions. Twelve(7%) of 158 patients had postoperative complications including wound complication, recurrence and facial nerve palsy.

Esophageal Atresia and Tracheoesophageal Fistula in Korea: A National Survery of Its Members by the Korean Association of Pediatric Surgeons

The first national survey on esophageal atresia and tracheoesophageal fistula was conducted to access the current status of its incidence. clinical manifestation, preoperative diagnosis and management, type of its anomaly, associated anomalies, and surgical results and course. The 43 members of the Korea Association of Pediatric Surgeons received questionnaires and registration forms to be filled out on each patient who were born during the three years from January I, 1992 through Decestricurember 31, 1994. Questionnaires composed of six broad areas which include 1) preoperative diagnosis and management, 2) surgical technic, 3) long gap, 4) postoperative management, and 5) complications and courses. A total of 148 cases was returned by 28 members working at 23 institutions and 27 members returped questionnaires. We obtained the following results by analysis of the 148 cases of tracheoesophageal anomalies. The incidence of tracheoesophageal anomaly was about 1/10,000-11,000 in 1994, which is one third of that of anorectal malformations in Korea and the distribution of the patients was almost proportionate to the size of each province. Both sexes are about equally affected. Majority of the members make diagnosis of tracheoesophageal anomaly by taking a simple infantogram with a radiopaque tube in upper pouch and a little under half(46%) prefers to perform echocardiography as a part of preoperative management to identify congenital heart disease and lateralize the aorta. Esophageal atresia with distal TEF(87.50/0) was by far the most common and threre were pure esopahgeal atresia(5.6%), H-type TEF(2.l%), and so on. About half(49%) of the patients had one or more associated anomalies in addition to tracheoesophageal anomalies. Congenital heart disease was associated in 46 cases(31 %), anorectral malfomations in 19 cases(13%), musculoskeletal anomalies in 15 cases(10%), genitourinary anomalies in 10 cases(7%) and gastrointestinal anomalies in 7 cases(5%). Postoperatively, parenteral nutrition and assisted ventilation were given in 66% and 52% of patients respectively. Ninety three(74%) of 126 cases who underwent surgical procedure, experienced one or more complications such as respiratory complication (65%), leak(22%), stricture(21%) and so on. The survival rates related to the Waterston risk categories were 90.2% in grpup A, 71.4-75% in B₁, B₂, and C groups, and 28% in group C₂ and the overall survival rate was 71.4%. Thirty six(28.6%) of 126 cases died of pneumonia/sepsis(12 cases), respiratory failure(l2 cases), and congenital heart disease(4 cases). With short term follow-up, 69% of patients have been excellent whereas remainders of the cases have suffered from some sort of morbidity related to gastroesophageal reflux, recurrent respiratory infection, and esophageal stricure.