A dose-finding study of lenograstim (glycosylated rHuG-CSF) for peripheral blood stem cell mobilization during postoperative adjuvant chemotherapy in patients with breast cancer. Lenograstim/Breast Cancer Study Group.
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BACKGROUND: The optimum dose of granulocyte colony-stimulating factor (G-CSF) for peripheral blood stem cell (PBSC) mobilization after disease-oriented, conventional-dose chemotherapy remains unknown. METHODS: A multicenter dose-finding study of glycosylated G-CSF (lenograstim) for the mobilization of PBSCs following adjuvant CAF chemotherapy (cyclophosphamide, doxorubicin and 5-fluorouracil) was performed in 38 patients with postoperative breast cancer. Each 10, ten and eight patients were sequentially allocated to one of the three dose groups (2, 5 and 10 micrograms/kg, respectively) of lenograstim. Lenograstim was administered subcutaneously (s.c.) daily from day 8 to the day of the last apheresis and CD34+ cells and colony-forming units-granulocyte macrophage (CFU-GMs) in peripheral blood were measured serially. Additionally, 10 patients who received adjuvant CAF chemotherapy alone also participated in the study, as a control. RESULTS: Lenograstim was well tolerated up to 10 micrograms/kg, except for one patient given 10 micrograms/kg who developed transient grade 3 hepatic enzyme elevation. The peak levels of CD34+ cells and CFU-GMs in peripheral blood showed dose-response relationships. The median peak CD34+ cells for the 0, 2, 5 and 10 micrograms/kg dose groups were 5.4, 34.3, 55.0 and 127.6 cells/microliter, respectively, and those of CFU-GMs for the 0, 2, 5 and 10 micrograms/kg dose groups were 0.01, 0.33, 1.32 and 3.30 CFU-GMs/microliter, respectively. CONCLUSIONS: Considering the previous reports suggesting that a pre-apheresis number of 40-50 CD34+ cells/microliter in peripheral blood is highly predictive for achievement of more than 2.5 x 10(6) CD34+ cells/kg in a standard apheresis procedure of 10 litres, the optimum dose of lenograstim for PBSC mobilization following CAF chemotherapy in patients with postoperative breast cancer is 5 micrograms/kg/day s.c. (+info)
Physical and psychological morbidity after axillary lymph node dissection for breast cancer.
(10/1289)
PURPOSE: Alternatives to axillary lymph node dissection (ALND) are being developed amid controversy surrounding the therapeutic benefit and overall utility of this routine surgical procedure. Although potential negative side effects associated with ALND are known, we set out to examine whether these side effects contribute significantly to patient reports of quality of life and mental health. PATIENTS AND METHODS: We surveyed 222 women who had received an ALND as part of breast cancer surgery. All women underwent a physical therapy assessment of range of arm/shoulder motion and completed the Modified Post-operative Pain Questionnaire, the Pain Disability Index, the McGill Pain Questionnaire (short form), the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, and the Mental Health Inventory. RESULTS: Seventy-two percent of the women experienced arm/shoulder pain, weakness, or numbness in the week before the interview, and range of motion of the affected arm/shoulder was impaired in 73% of the women. Severity of pain was reported to be low to moderate, and younger patients experienced greater pain than older patients. Pain severity correlated positively with the number of lymph nodes removed and receipt of chemotherapy and was not significantly related to length of time since surgery or receipt of radiation therapy. Generally high levels of cancer-specific quality of life and mental health were reported. Quality of life was significantly predicted by the McGill Pain Questionnaire, and mental health was significantly predicted by the Pain Disability Index and the physical therapy assessment. CONCLUSION: Surgery-related symptoms after ALND persist for a majority of women with breast cancer and are not significantly related to time since surgery or receipt of radiation therapy. These symptoms and associated disability are significantly predictive of cancer-specific quality of life and mental health. (+info)
Initial experience with breast reconstruction using the transverse rectus abdominis myocutaneous flap: a study of 45 patients.
(11/1289)
Breast conserving surgery for breast cancer has led to an increased interest in reconstruction following mastectomy. The transverse rectus abdominis myocutaneous flap has been proven to give good results in terms of restoration of body symmetry with near normal contour and consistency. Furthermore, immediate reconstruction has the advantage of a single procedure with less psychological morbidity, and reduction in hospital stay and overall complication rate. The aim of this study was to review our experience with the transverse rectus abdominis myocutaneous flap procedure an initial series of 45 patients. The overall complication rate of 27% is similar to that reported in the literature, with no total flap loss and nine patients with partial flap loss. There was no delay in commencement of adjuvant chemotherapy or radiotherapy and we believe our ability to detect local recurrence has not been compromised. We consider that immediate breast reconstruction is now an integral part of the surgical treatment of breast cancer. (+info)
Gynecomastia and mammary gland adenocarcinoma in a Nubian buck.
(12/1289)
A 6-year-old Nubian buck was presented for bilateral mammary gland enlargement. Gynecomastia and mastitis were diagnosed, and bilateral mastectomy was performed. Histological examination showed mammary adenocarcinoma, active lactation, hyperplasia, and abscessation. Karyotyping showed a normal male. Clinical, therapeutic, etiologic, and epidemiologic aspects of gynecomastia and mammary gland adenocarcinoma are discussed. (+info)
First-line high-dose sequential chemotherapy with rG-CSF and repeated blood stem cell transplantation in untreated inflammatory breast cancer: toxicity and response (PEGASE 02 trial).
(13/1289)
Despite the generalization of induction chemotherapy and a better outcome for chemosensitive diseases, the prognosis of inflammatory breast cancer (IBC) is still poor. In this work, we evaluate response and toxicity of high-dose sequential chemotherapy with repeated blood stem cell (BSC) transplantation administered as initial treatment in 100 women with non-metastatic IBC. Ninety-five patients (five patients were evaluated as non-eligible) of median age 46 years (range 26-56) received four cycles of chemotherapy associating: cyclophosphamide (C) 6 g m(-2) - doxorubicin (D) 75 mg m(-2) cycle 1, C: 3 g m(-2) - D: 75 mg m(-2) cycle 2, C: 3 g m(-2) - D: 75 mg m(-2) - 5 FU 2500 mg m(-2) cycle 3 and 4. BSC were collected after cycle 1 or 2 and reinfused after cycle 3 and 4. rG-CSF was administered after the four cycles. Mastectomy and radiotherapy were planned after chemotherapy completion. Pathological response was considered as the first end point of this trial. A total of 366 cycles of chemotherapy were administered. Eighty-seven patients completed the four cycles and relative dose intensity was respectively 0.97 (range 0.4-1.04) and 0.96 (range 0.25-1.05) for C and D. Main toxicity was haematological with febrile neutropenia ranging from 26% to 51% of cycles; one death occurred during aplasia. Clinical response rate was 90% +/- 6%. Eighty-six patients underwent mastectomy in a median of 3.5 months (range 3-9) after the first cycle of chemotherapy; pathological complete response rate in breast was 32% +/- 10%. All patients were eligible to receive additional radiotherapy. High-dose chemotherapy with repeated BSC transplantation is feasible with acceptable toxicity in IBC. Pathological response rate is encouraging but has to be confirmed by final outcome. (+info)
Enhanced prediction of breast cancer prognosis by evaluating expression of p53 and prostate-specific antigen in combination.
(14/1289)
p53 gene mutation is the most common genetic alteration in neoplastic diseases, including breast cancer, for which p53 alteration may indicate poor prognosis. Recent clinical evidence suggests that prostate-specific antigen (PSA) expression may identify breast cancer patients with favourable outcome. Assessment of p53 and PSA in combination, potentially offering improved prediction, has not yet been performed. Extracts from 952 primary breast carcinomas were assayed for PSA and p53 by quantitative enzyme-linked immunosorbent assays (ELISAs) developed by the authors. Concentrations of each marker were classified as negative or positive on the basis of median and 30th percentile cut-off points for p53 and PSA respectively. Patients followed for a median of 6 years having different combinations of negative or positive status for PSA and p53 were compared with respect to the relative risks (RRs) for relapse and death by Cox proportional hazards regression analysis, in which an interaction term was also evaluated, and with respect to disease-free survival (DFS) and overall survival (OS) probabilities by Kaplan-Meier plots and log-rank tests. Multivariate models were adjusted for oestrogen and progesterone receptor status, nodal status, patient age, tumour size, DNA ploidy, S phase fraction and receipt of chemotherapy. Interactions were not found between the status of PSA and p53 in the Cox models, in which PSA-negativity (RR = 1.47, P = 0.020 for DFS, and RR = 1.49, P = 0.023 for OS) and p53-positivity (RR = 1.46, P = 0.017 for DFS, and RR = 1.41, P = 0.033 for OS) were individually associated with prognosis. Evaluation of a combined three-level variable revealed that PSA(-)/p53(+) patients had significantly higher risks for relapse (RR = 2.13, P < 0.001) and death (RR = 2.08, P = 0.001) than PSA(+)/p53(-) patients, and that patients positive or negative for both markers had intermediate risks for the outcome events in the same multivariate analysis (RR = 1.45 for both DFS and OS). The results of our study demonstrate that the assessment of combined PSA and p53 expression status by ELISAs, easily applicable to breast tumour extracts prepared for steroid hormone receptor analyses, may stratify breast cancer patients into groups differing by relapse and death risks of greater magnitude than offered by the assessment of either p53 or PSA alone. (+info)
Autologous stem-cell transplant after conventional dose adjuvant chemotherapy for high-risk breast cancer: impact on the delivery of local-regional radiation therapy.
(15/1289)
BACKGROUND: High-dose chemotherapy with autologous stem-cell transplantation is used increasingly in the treatment of poor-prognosis primary breast cancer. Because these patients may be cured with standard multimodality therapy, it is important to address both the efficacy of transplantation, and its effect on the delivery of standard treatments including local radiation therapy. PATIENTS AND METHODS: Patients with high risk primary breast cancer were treated with high-dose cyclophosphamide and thiotepa and stem-cell transplant following surgery and conventional-dose adjuvant chemotherapy. Outcome, including sites of failure and delivery of local radiation therapy, was assessed for 103 patients. RESULTS: Overall and disease-free survival rates at 18 months were 83% (+/- 4%) and 77% (+/- 4%) respectively. Twenty patients (19.4%) received radiation therapy prior to transplant. Of the remaining 83, 77 received radiation therapy after transplant. Overall, 5 (19.2%) of 26 first sites of recurrence were local alone. For patients receiving radiation prior to transplant, 3 of 7 (43%, 95% CI: 6%-80%) sites of first recurrence were local, while 2 of 19 (10.5%, 95% CI: 0%-24.5%) sites of first recurrence were local alone in patients receiving post-transplant radiation or no radiation. CONCLUSION: Transplantation does not appear to significantly compromise the delivery or outcome of local radiation therapy for primary breast cancer. (+info)
Surgical treatment of early breast cancer: what would surgeons choose for themselves?
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CONTEXT: Although breast-conserving surgery (BCS) is less invasive than mastectomy and results in similar survival, many women eligible for BCS continue to undergo mastectomy. Whether the persistent use of mastectomy means that women do not understand their options or reflects an informed preference is unknown. OBJECTIVE: To learn which treatment surgeons would choose when asked to imagine that they themselves had early-stage breast cancer. DESIGN: Cross-sectional survey. SAMPLE: Convenience sample of 40 staff and resident surgeons attending surgical grand rounds at Dartmouth-Hitchcock Medical Center in 1998. MAIN OUTCOME MEASURE: Choice of BCS or mastectomy for the treatment of stage I breast cancer. RESULTS: Twenty-six male and 14 female surgeons participated in the survey. Half chose BCS and half chose mastectomy for treatment of their hypothetical early-stage breast cancer. Results did not differ by the sex of the surgeon. CONCLUSION: Even after being reminded of the equivalent 10-year survival statistics, half of the surgeons surveyed said that they would choose mastectomy over BCS for themselves. The assumption that BCS is the "right" choice for early-stage breast cancer may be unwarranted because many patients may have an informed preference for mastectomy. (+info)