Male breast cancer: a survey at the Helsinki University Central Hospital during 1981-2006.

BACKGROUND: The purpose was to analyze the behavior of male breast cancer. METHODS: Fifty-eight male breast cancer patients were treated at the HUCH during 1981-2006. Data on risk factors, tumor characteristics, clinical presentation, treatment and survival were obtained by chart review. RESULTS: Presentation occurred at a median age of 63 years, most often due to a self-detected lump. The median size of the primary tumor was 1.8 cm and 14% were T4 tumors. Forty-seven percent had lymph node metastases and 4% distant metastases at diagnosis. Ductal carcinoma was the most common tumor type. All tumors with known receptor status were positive for estrogen receptor (ER) and 79% for progesterone receptor (PgR). Her-2 overexpression was found in 2/19 patients (11%). A family history of breast cancer, obesity, high alcohol intake and liver cirrhosis were the most often seen risk factors. Nineteen percent had one or two other malignancies, the most common second malignancy being prostate cancer in 7%. Ninety-seven percent were operated by mastectomy and 90% by axillary evacuation while sentinel node biopsy alone was done only in 7%. Sixty percent of the patients received radiotherapy, 64% adjuvant hormonal treatment, 20% adjuvant chemotherapy, and 2% adjuvant trastuzumab. Fourteen patients (25%) experienced a relapse of which 60% were distant, bone being the most common site. During follow-up 21 patients (37%) died, of whom nine of breast cancer and 12 due to other causes. The 5-year overall survival (OS) was 75%. CONCLUSIONS: Male breast cancer behaves and is today treated in many respects like postmenopausal breast cancer. However, due to rudimentary breast tissue the symptoms, diagnosis and especially a higher amount of T4 tumors differ from that of females. Also the risk factor profile and histologic subgroups seem different. The 5-year OS of 75% is clearly higher than 44% reported at our institution in 1982.

The expression of p53, bcl-2, bax, fas and fasL in the primary tumour and lymph node metastases of breast cancer.

PURPOSE. It is unknown to what extent lymph node metastases differ from primary tumours of breast cancer. Our aim was to investigate the similarity between primary breast tumours and the matching lymph node metastases in 59 breast cancer patients. EXPERIMENTAL DESIGN. Immunohistochemical stainings of p53, bax, bc-l2, fas and fasL were performed in primary tumours and the parallel lymph node metastases. RESULTS. When using a cut point of 10%, the concordance between primary tumours and parallel lymph node metastases in the expression of p53 was 85%, bcl-2 79%, bax 69%, fas 59% and fasL 43%. In most tumours the staining status of p53, bcl-2 and bax in the primary tumour and the corresponding lymph node did not change more than 20%. However, these variables could fluctuate in both directions. In 15-25% of the cases, nodal expression was more than 20% lower than in the primary tumours, while in 10-17% of the cases, nodal expression was more than 20% higher than in the primary tumours. In half of the tumours, fas status did not change. Most fasL positive tumours lost positivity in the lymph node metastases or showed positively staining cancer cells only in the peripheral region of the node. A phenotype analysis of combined information of tumour fas/tumour fasL/nodal fas/nodal fasL expression (+/ - ) was assessed. The most frequently observed phenotype was tumour fas - /tumour fasL + /nodal fas - /nodal fasL- (22% of the tumours), although almost all combinations were seen. CONCLUSIONS. The expression of p53, bax, bcl - 2, fas and fasL is not maintained in the matching lymph node metastases of breast cancer. Large studies comparing the expression of relevant tumour biology factors in primary tumours and parallel lymph node metastases and their impact on therapy outcome, especially in the adjuvant setting, are warranted.

A phase I study of an all-oral combination of vinorelbine/capecitabine in patients with metastatic breast cancer previously treated with anthracyclines and/or taxanes.

BACKGROUND: Few overlapping toxicities and oral formulations make capecitabine plus oral vinorelbine an attractive new combination for treating patients with breast cancer. An all-oral regimen minimizes inconvenience for the patient and saves medical resources. PATIENTS AND METHODS: To determine the recommended dose for this all-oral combination, we conducted a phase I study in 21 patients with metastatic breast cancer after failure of previous chemotherapy with anthracylines and/or taxanes for advanced disease. Capecitabine 1000 mg/m2 twice daily was given on days 2-7 and 9-14. Vinorelbine was administered at escalating doses of 40-80 mg/m2 on days 1 and 8 every 3 weeks. Dose escalation of vinorelbine was performed in cohorts of 3 patients, but the dose of vinorelbine could also be increased to the next level in the same patient after 3 cycles if there were no dose-limiting toxicities. In total, 173 cycles were administered (median, 8 cycles; range 1-21+ cycles). RESULTS: Treatment was well tolerated: there were no grade 4 toxicities, and the only grade 3 toxicities in > 1 cycle were hand-foot syndrome and neutropenia (2% of cycles each). The maximum tolerated dose could not be determined using predefined criteria. However, in this heavily pretreated patient population, intrapatient vinorelbine dose escalation > 60 mg/m2 was rarely achieved. Thus, we considered vinorelbine 60 mg/m2 to offer the best dose level-toxicity ratio. At this dose, grade 3 toxicities occurred in only 7% of the 58 cycles administered. Among 19 evaluable patients, 7 exhibited response or stable disease lasting > 6 months, giving a clinical benefit rate of 37%. Duration of response in the 2 responding patients was 5 months and > 16 months. CONCLUSION: The all-oral combination of capecitabine/vinorelbine is well tolerated and active in heavily pretreated patients. Oral vinorelbine 60 mg/m2 is recommended in combination with capecitabine 1000 mg/m2 twice daily for further evaluation.