Expression and clinical relevance of p-glycoprotein (p-gp) were evaluated in 31 cases of locally advanced breast cancer and 9 cases involving inflammatory breast cancer after induction chemotherapy. The de novo p-gp expression rate was 26% and increased up to 58% (p = 0.03) with the FAC (5-fluorouracil, adriamycin, cyclophosphamide) regimen. Although more clinically complete responders were found in the secondary p-gp negative group (p = 0.02), this difference was not found in pathological tumor response. Moreover, as the grade of the secondary p-gp expression increased, the chemotherapeutic effect decreased, suggesting an inverse relationship between p-gp expression and drug effect (p = 0.04). When we subgrouped the patients into 4 groups using these two parameters, p-gp negative patients presenting with a high drug effect showed a low recurrence rate (p = 0.05) and marginal survival benefits (p = 0.09) as opposed to patients with a low drug effect. But in p-gp positive groups, the recurrence rate was the same between the two groups regardless of the drug effect. Thus, in the p-gp negative patient with a high drug effect, adjuvant chemotherapy with the same regimen as induction chemotherapy may induce more prognostically favorable results. Therefore, clinical application of the secondary p-gp detection can be used as an intermediate endpoint in evaluating drug response for an induction regimen.
We have studied the patterns of P-glycoprotein expression before and after 3 cycles of induction chemotherapy (5-fluorouracil, adriamycin and cyclophosphamide) using immunohistochemically stained paraffin-embedded specimen of 28 patients with locally advanced breast cancer. The frequency of P-glycoprotein expression in untreated breast cancer turned out to be very low: only one out of 28 untreated, biopsy specimen at the time of diagnosis was positive. The frequency of P-glycoprotein expression was markedly increased from 9.1% before chemotherapy to 63.6% after induction chemotherapy (p = 0.006). After 3 cycles of induction chemotherapy, 25 patients had obtained clinical response to chemotherapy (4, CR; 21, PR). Eleven out of 25 tumors (44%) showing clinical response and all three tumors (100%) with minimal response have expressed P-glycoprotein. One out of 6 patients (16.7%) with microscopic residual tumor seen in mastectomy specimen expressed P-glycoprotein, whereas 13 of 22 patients (59.1%) with gross residual tumor showed the presence of P-glycoprotein (p = 0.08). The frequency of intrinsic P-glycoprotein expression in untreated breast cancer was quite low, but approximately half of the patients do acquire P-glycoprotein expression during the cycles of induction chemotherapy. Therefore, the results suggest that the immunohistochemical detection of P-glycoprotein on residual tumor cells after induction chemotherapy can predict acquired drug resistance in breast cancer.
Sixteen cases of male breast cancer seen over a 20-year period were reviewed. The causes of cancer of the male breast are no better understood, but major alterations in hormonal environment could be a significant factor. Some clinical characteristics correspond well with the results of other series. The median age at presentation was 61.7 years. The most frequent initial symptom was a painless mass, and the incidences of nipple discharge, central tumor location, and axillary node involvement were high. Males also had a higher incidence of local advancement which was associated with a longer delay in seeking treatment and small breast tissue. The pathologic type was infiltrating ductal type in all cases except one, and all cases showed favorable nuclear grade. Estrogen receptor analysis was performed from the tumor of 2 patients. Both of them showed a high receptor level. There was no locoregional relapse in 5 patients who received adjuvant radiotherapy in contrast to the 2 relapses in 3 patients who underwent surgery alone. And three of the five patients who received radiotherapy suffered from systemic metastasis which suggested the important role of adjuvant chemotherapy as well as radiotherapy. In light of the encouraging results about adjuvant chemotherapy in the treatment for female breast cancer with axillary lymph node involvement, it would be desirable to extend this policy to male breast cancer.
Gastric cancer is the most common cause of cancer related death in Korea. Early gastric cancer (EGC), confined to mucosa or submucosa, regardless of lymph node metastasis, is known to have a favorable prognosis. From 1976 to 1995, four thousand nine hundred and twenty eight gastric cancer patients underwent operation at the Severance Hospital, Yonsei University, College of Medicine, Seoul, Korea. Of these, 1,117 patients (22.6%) were diagnosed as EGC and underwent curative operation. Clinicopathologic characteristics were reviewed and survival data was analyzed. The proportion of EGC has increased during the last two decades, from 14.9% during 1976-1985 to 25.8% for 1986-1995. EGC has a wide age distribution range from the thirties to the sixties, with highest incidence in the sixties. The male to female ratio is 1.8:1, without any significant change in last two decades. Most lesions are located in the lower third of stomach (52.3%), and the lesser curvature (52.2%) was the most frequent site in the transverse axis. Macroscopically, the depressed type was the most common (66.1%) followed by the elevated, flat and mixed types, in that order. Tumor confined to the mucosa layer was seen in 52.5%, and lymph node involvement in 11.7%. The depth of tumor invasion correlated with tumor size and regional lymph node involvement. On histopathologic examination, signet ring cell type accounted for 29.6% of all EGCs. Overall 5-year survival rate was 92.7% and the presence of lymph node metastasis significantly affected survival (84.6% versus 96.2%) (p<0.05). In conclusion, the proportion of EGC, in terms of the gastric cancers operated upon, has been increasing in Korea over the last two decades. The introduction of active diagnostic approaches and diagnostic modalities could improve early diagnosis and the cure rate of gastric cancer in Korea.
Positive metabolic activity of uveal melanoma based on the positron emission tomography/computed tomography was significantly associated with rapid initial tumor regression after combined plaque radiotherapy and thermotherapy, suggesting a prognostic value for this diagnostic approach.
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