Clinical analysis of 276 cases of non-palpable TO breast cancer

Objective Discussion of diagnosis, treatment and prognosis of non-palpable TO breast cancer. Methods Between 1978 and 1997, 9,980 female patients with operable breast cancer were treated surgically, of which 276 were determined to have TO breast cancer. Most TO breast cancers could be detected promptly with careful examination of presenting symptoms, such as nipple discharge, local thickening of the breast, nipple erosion, nipple retraction and postmenopausal mastalgia, while 12 cases were detected by routine mammography of the contralateral breast. Results All patients were treated surgically and their tissue subjected to histopathological examination. Most cases (73.0%) were noninvasive or early invasive carcinoma. Axillary lymph nodes metastases were found in 7.69% of 234 mastectomy cases. Conclusion The survival rate was significantly increased if the tumor was in an early stage. The 5-, 10-, 15-years survival rates were 98.1%, 94.6% and 90.3%, respectively.     

男性乳癌特征分析(附31例报告)

目的：了解男性乳癌特点，提高其早期诊断率及治疗效果。方法：对31例男性乳癌进行了回顾性分析。结合随访资料，应用Kaplan-Meier法进行生存分析。结果：男性乳癌少见，病因不清，发病多在50岁以上，临床病例晚期多见，容易侵犯皮肤及胸肌，乳头常受累，可伴乳头溢血，淋巴结转移较早，雌激素受体阳性率高，治疗以手术为主，主要是改良根治术，包括化疗，内分泌治疗和放疗的综合治疗，预后与腋淋巴结转移状况有关。结论：男性乳癌晚期多见，治疗以综合治疗为主。预后与腋淋巴结转移状况相关。     

Double-blind randomised trial comparing the non-steroidal aromatase inhibitors letrozole and fadrozole in postmenopausal women with advanced breast cancer.

BACKGROUND: To compare the efficacy, safety and tolerability of letrozole, an advanced non-steroidal aromatase inhibitor, and fadrozole hydrochloride, an older-generation drug in this class, we conducted a randomised double-blind trial in postmenopausal women with advanced breast cancer. PATIENTS AND METHODS: One hundred and fifty-seven postmenopausal women with advanced breast cancer were enrolled and randomly assigned to receive letrozole or fadrozole in a multicentre, randomised double-blind trial in Japan. One hundred and fifty-four eligible patients were treated with either letrozole 1.0 mg once daily (n = 77) or fadrozole 1.0 mg twice daily (n = 77), for a minimum of 8 weeks. RESULTS: Letrozole showed a significantly higher overall objective response rate [complete response (CR) + partial response (PR)] than fadrozole (31.2% and 13.0%, respectively; P = 0.011, Fisher's exact test). Clinical benefits defined as CR, PR and stable disease (no change in status for more than 24 weeks) were also higher in patients treated with letrozole (50.6%) than fadrozole (35.1%). Letrozole was significantly superior to fadrozole in terms of the dominant lesion in soft tissue, bone and viscera (P = 0.011, stratified Mantel-Haenszel test). Median time to progression was 211 days in the letrozole group and 113 days in the fadrozole group with no significant difference (P = 0.175, log-rank test). Letrozole markedly reduced the estradiol, estrone and estrone sulfate levels in peripheral blood within 4 weeks. The suppressive effect of fadrozole on these hormone levels was insufficient. Adverse drug reactions were observed in 35.9% of the patients treated with letrozole and in 39.5% of those treated with fadrozole with no significant difference between the two groups (P = 0.74, Fisher's exact test). Most of the adverse drug reactions were rated as grade 1 or 2. CONCLUSIONS: The results show letrozole at a dose of 1.0 mg once daily to be more effective in treating postmenopausal women with advanced breast cancer than fadrozole at 1.0 mg twice daily, with similar safety and tolerability profiles.     

Randomized controlled trial comparing oral doxifluridine plus oral cyclophosphamide with doxifluridine alone in women with node-positive breast cancer after primary surgery.

PURPOSE: We compared the therapeutic usefulness of doxifluridine (5'-DFUR) alone and a combination of 5'-DFUR plus cyclophosphamide (CPM), both of which are considered effective against advanced and recurrent breast cancer, to determine which treatment is more beneficial as postoperative adjuvant chemotherapy. PATIENTS AND METHODS: A total of 1,131 women with node-positive primary breast cancer were randomly assigned after primary surgery to receive 5'-DFUR alone or 5'-DFUR plus CPM. All patients initially received 5'-DFUR in an oral dose of 1,200 mg/d for 4 weeks, starting 4 weeks after surgery. Chemotherapy was then not given for 2 weeks. Patients in the 5'-DFUR group subsequently received five 4-week cycles of treatment consisting of oral 5'-DFUR (1,200 mg/d) for the first 2 weeks and no chemotherapy for the next 2 weeks. Those assigned to the 5'-DFUR plus CPM group also received oral CPM 100 mg/d for the first 2 weeks and no chemotherapy for the next 2 weeks. Women 50 years or older concurrently received 20 mg/d of tamoxifen for 2 years in both groups. RESULTS: Of the 1,088 eligible women, 546 were assigned to receive 5'-DFUR alone and 542 were assigned to receive 5'-DFUR plus CPM. Overall disease-free survival was significantly better in women who received 5'-DFUR plus CPM than in those who received 5'-DFUR alone (log-rank test, P =.021). Toxic effects occurred in 20.0% of patients (109 of 546) in the 5'-DFUR group and 32.3% of patients (175 of 542) in the 5'-DFUR plus CPM group (chi(2) test, P <.001). CONCLUSION: Combination therapy with 5'-DFUR plus CPM is more effective in preventing recurrence than 5'-DFUR alone.     

Psychosocial Support for Women with Advanced Breast Cancer

Women with advanced breast cancer frequently experience psychologic distress as a result of their illness and its treatment. This distress may be manifest as depression, anxiety, symptoms of the stress-response syndrome, difficulty coping and social isolation. Six randomized trials of psychosocial interventions have been conducted in metastatic breast cancer. Five of these evaluated group psychosocial support – supportive-expressive therapy in three studies, cognitive-behavioral in one, and a combination of cognitive-behavioral and supportive therapy in another. All of these studies identified psychological benefits, notably improvement in mood, pain control and coping, although benefits were small in one study that provided the control group with a home cognitive-behavioral study program. One study identified an unexpected survival benefit associated with a group intervention – three subsequent studies have failed to replicate this result. Survival results of one additional ongoing study are pending.Studies in early breast cancer, and in patients with a spectrum of other cancers, have demonstrated benefits of individual psychological interventions, educational interventions and relaxation/self-hypnosis/imagery interventions, however, these have not been adequately evaluated in metastatic breast cancer.Based on these results, it is recommended that psychosocial support be offered to women with advanced breast cancer. Current research does not provide sufficient information to determine the optimal type of intervention to be used, or the optimal timing and duration of such interventions. Furthermore, it is not clear which patients benefit the most from psychosocial intervention and whether there are some patients who do not require psychosocial intervention. Research to address these issues is recommended.     

Reduced apoptosis and proliferation and increased Bcl-2 in residual breast cancer following preoperative chemotherapy

Experimental laboratory data suggest that tumour growth is a balance between apoptosis and proliferation and that suppression of drug-induced apoptosis by oncogenes such as bcl-2 may be an important cause of intrinsic chemoresistance. The aims of this study were to assess the in vivo relationship of apoptosis to proliferation and Bcl-2 protein in human breast tumours both prior to chemotherapy and in the residual resistant cell population at the completion of treatment. We examined apoptotic index (AI), Ki67 and Bcl-2 protein expression in the tissue of 40 patients with operable breast cancer immediately before ECF preoperative chemotherapy, and in 20 of these patients with residual tumour, at the completion of treatment. There was a significant positive association between AI and Ki67 both before and after chemotherapy, and in their percentage change with treatment. In the residual specimens AI and Ki67 were significantly reduced compared with pre-treatment biopsies, while Bcl-2 expression showed a significant increase. No differences were seen in the pre-treatment levels of any of the variables measured between patients obtaining pathological complete response and those who did not, although numbers were small. These data suggest that apoptosis and proliferation are closely related in vivo. It is possible that the phenotype of reduced apoptosis and proliferation, and increased Bcl-2 may be associated with breast cancer cells resistant to cytotoxic chemotherapy, although this can only be proven by assessing larger numbers of patients in relation to pathological response.