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| Au: Costa LA; Kopreski MS; Demers LM; Chinchilli VM; Santen RJ; Harvey HA; Lipton A. ----- Ti: Effect of the potent aromatase inhibitor fadrozole hydrochloride (CGS 16949A) in postmenopausal women with breast carcinoma. ----- So: Cancer. 85(1):100-3, 1999 Jan 1. ----- Ab: BACKGROUND: Fadrozole hydrochloride (CGS 16949A) is a highly potent, nonsteroidal aromatase inhibitor that significantly lowers estrogen levels in postmenopausal women and can be effective therapy for patients with advanced hormone-dependent breast carcinoma. Circulating estradiol, estrone, and estrone sulfate are reduced to undetectable levels within weeks of the initiation of therapy. Before this study, it was not known whether this decrease in serum estrogen levels results in altered parameters associated with cardiovascular disease. The authors examined the levels of several critical blood parameters that are important to cardiovascular risk for heart disease and thromboembolic disorders in patients treated with fadrozole. METHODS: Cholesterol, triglyceride, low density lipoprotein (LDL), high density lipoprotein (HDL), very low density lipoprotein (VLDL), antithrombin III, protein C, protein S, and fibrinogen were serially measured in 21 postmenopausal women with advanced breast carcinoma treated with various doses of fadrozole (1.8 mg/day, n=3; 2.0 mg/day, n=13; 4.0 mg/day, n=5) over 3-24 months (mean, 15.8 months). A repeated measure analysis of variance was applied to each cardiovascular variable to assess changes in the response over time. Analyses were performed separately for each dose group and were also pooled over the dose groups. RESULTS: There was no statistically significant change over time in lipid parameters, namely, total cholesterol (P=0.57), triglyceride (P=0.27), LDL (P=0.99), HDL (P=0.30), and VLDL (P=0.43), over the 24 months of therapy. There were also no significant changes in coagulation factors, namely, antithrombin III (P=0.41), protein C (P=0.49), or protein S (P=0.31), over the 24 months. However, an increase in fibrinogen that occurred over time did reach statistical significance (P=0.011). CONCLUSIONS: With the exception of acute phase reactant fibrinogen, this study did not identify an increase in parameters associated with cardiovascular disease in women treated with fadrozole, a potent aromatase inhibitor (Au). |
| Au: Rahman ZU; Frye DK; Smith TL; Asmar L; Theriault RL; Buzdar AU; Hortobagyi GN. ----- Ti: Results and long term follow-up for 1581 patients with metastatic breast carcinoma treated with standard dose doxorubicin-containing chemotherapy: a reference. ----- So: Cancer. 85(1):104-11, 1999 Jan 1. ----- Ab: BACKGROUND: The authors report results and long term follow-up for 1581 patients with metastatic breast carcinoma treated with doxorubicin-containing combination chemotherapy at a single institution; this report is meant to serve as a reliable reference for single-arm studies of newer therapies in this patient population. METHODS: Prospectively collected data from 18 successive doxorubicin-containing protocols for the treatment of metastatic breast carcinoma were evaluated. RESULTS: The response rate was 65.0% (95% confidence interval [CI]: 62.5-67.3%), complete response (CR) rate was 16.6% (95% CI: 14.8-18.6%), and partial response (PR) rate was 48.5% (95% CI: 46.0-50.9%). Median progression free survival (PFS) was 11.5 months (95% CI: 10.9-12.3 months) and median overall survival (OS) was 21.3 months (95% CI: 20.3-22.7 months). Survival correlated with response to therapy; median PFS and OS were 22.4 and 41.8 months, respectively, for the patients who achieved CR (n=263) and 14 and 24.6 months, respectively, for PR patients (n=766). The median OS of patients who had progressive disease during chemotherapy was 3.8 months. The response rate, PFS and OS correlated with number of organs involved and especially with tumor burden. Patients with hormone receptor-positive tumors had a similar response rate to that of patients with hormone receptor negative tumors but had significantly longer PFS (medians of 14.3 and 8.7 months, respectively) and OS (medians of 28.6 and 18.1 months, respectively). CONCLUSIONS: In patients with metastatic breast carcinoma, doxorubicin-containing chemotherapy had a response rate of 65% and a CR rate of 16.6%. PFS and OS were 11.5 months and 21.3 months, respectively, for all responders and 22.4 months and 41.8 months, respectively, for those who had CR (Au). |
| Au: Mikhak B; Zahurak M; Abeloff MD; Fetting JH; Davidson NE; Donehower RC; Waterfield W; Kennedy MJ. ----- Ti: Long term follow-up of women treated with 16-week, dose-intensive adjuvant chemotherapy for high risk breast carcinoma. ----- So: Cancer. 85(4):899-904, 1999 Feb 15. ----- Ab: BACKGROUND: A Phase II study was performed evaluating the disease free and overall survival rates associated with a dose-intensive, 16-week, doxorubicin-based adjuvant chemotherapy regimen in women with breast carcinoma and > or = 10 involved axillary lymph nodes. METHODS: Eligible patients underwent staging with computed tomography and bone scanning and were treated with a 16-week, dose-intensive chemotherapy regimen, comprised of 8 2-week courses of cyclophosphamide, 100 mg/m2 orally, on Days 1-7; doxorubicin, 40 mg/m2 intravenously (i.v.), on Day 1; methotrexate, 100 mg/m2 i.v., on Day 1 with leucovorin rescue, 10 mg/m2, every 6 hours for 6 doses orally on Day 2; vincristine, 1 mg i.v. on Day 1; 5-fluorouracil (5-FU), 600 mg/m2 i.v., on Day 2 over 2 hours; and 5-FU, 300 mg/m2/day continuous i.v. on Days 8 and 9. Tamoxifen, 20 mg daily, was administered to patients with estrogen receptor positive tumors treated after October 1988. All patients were offered locoregional radiation therapy. RESULTS: Sixty-four women were treated on protocol. The median follow-up of 27 surviving patients was > 8 years at last follow-up. Three patients were lost to follow-up. The median time to progression was 54 months, the Kaplan-Meier estimate of event free survival at 5 years was 44% (95% confidence interval [CI], 31-56%), and the Kaplan-Meier estimate of overall survival at 5 years was 57% (95% CI, 44-69%). At 98 months the Kaplan-Meier estimate of freedom from recurrence was 31% (95% CI, 19-43%) and the Kaplan-Meier estimate of survival at 111 months was 36% (95% CI, 23-49%). CONCLUSIONS: Despite the use of dose-intensive, doxorubicin-based, adjuvant chemotherapy, and intensive staging prior to study entry, the results of the current study are similar to those of previous reports for standard dose chemotherapy and appear inferior to those reported for high dose therapy (Au). |
| Au: Blajman C; Balbiani L; Block J; Coppola F; Chacon R; Fein L; Bonicatto S; Alvarez A; Schmilovich A; Delgado FM. ----- Ti: A prospective, randomized Phase III trial comparing combination chemotherapy with cyclophosphamide, doxorubicin, and 5-fluorouracil with vinorelbine plus doxorubicin in the treatment of advanced breast carcinoma. ----- So: Cancer. 85(5):1091-7, 1999 Mar 1. ----- Ab: BACKGROUND: A prospective, multicenter, randomized, Phase III trial comparing the efficacy of combination chemotherapy with 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) with a combination of vinorelbine and doxorubicin (NA) in the treatment of patients with advanced breast carcinoma was undertaken. METHODS: One hundred and seventy-seven patients who previously were untreated for recurrent or metastatic breast carcinoma were entered into the study; 7 patients could not be assessed. The final analysis relates to 85 patients who were treated with FAC and 85 patients who were treated with NA, of whom 21 (25%) and 44 (52%), respectively, had received prior adjuvant chemotherapy. RESULTS: The overall response rates were similar for the two treatments and were unaffected by prior exposure to adjuvant therapy; overall response rate (ORR) for FAC was 74% (95% confidence interval [95% CI], 65-83%), and the ORR for NA was 75% (95% CI, 66-84%). The activity of NA in patients with liver involvement was greater than that of FAC in terms of survival. Overall survivals were similar, with a median of 17.3 months for patients receiving FAC and 17.8 months for patients receiving NA. Severe toxicity was uncommon with World Health Organization Grade 3-4 neutropenia affecting only 7% of patients in each arm of the study. NA was associated with a higher incidence of mild to moderate constipation, neurotoxicity, and phlebitis, whereas FAC produced a slight excess of mild cardiotoxicity. CONCLUSIONS: The efficacy of these two regimens is very similar, although NA may be more active in a subset of patients with visceral metastatic disease, particularly liver involvement. It is clear that, in a direct comparison with an established three-drug regimen, the newer two-drug combination of NA demonstrated equivalent activity with no significant excess of Grade 3-4 toxicity (Au). |
| Au: Ingle JN; Suman VJ; Kardinal CG; Krook JE; Mailliard JA; Veeder MH; Loprinzi CL; Dalton RJ; Hartmann LC; Conover CA; Pollak MN. ----- Ti: A randomized trial of tamoxifen alone or combined with octreotide in the treatment of women with metastatic breast carcinoma. ------ So: Cancer. 85(6):1284-92, 1999 Mar 15. ----- Ab: BACKGROUND: Tamoxifen (TAM) is generally considered the hormonal agent of choice for postmenopausal women with hormone receptor positive breast carcinoma. The somatostatin analogues, including octreotide, have demonstrated inhibition of breast carcinoma cell lines and multiple endocrinologic actions, including reduction of insulin-like growth factor I (IGF-I), a potent mitogen for breast carcinoma cells. In an attempt to improve the efficacy of TAM, this randomized trial was performed. METHODS: One hundred thirty-five eligible postmenopausal women with metastatic breast carcinoma were randomized to TAM (10 mg twice daily) alone or combined with octreotide 150 microg (administered subcutaneously thrice daily). The two groups were well balanced, except the TAM group had higher proportions of patients with visceral disease (50% vs. 37%) and a disease free interval longer than 5 years (47% vs. 34%). A cohort of 18 patients was evaluated for the impact of treatment on serum IGF-I, free IGF-I, IGF binding protein 3 levels, and total IGF binding capacity. RESULTS: The median time to progression was estimated to be 14.2 months with TAM and 10.3 months with TAM plus octreotide. The distribution of progression free survival times revealed no significant difference (P = 0.26), and the progression hazard ratio (TAM/TAM + octreotide) was 0.81 (95% confidence interval [CI], 0.56-1.17). The distribution of survival times revealed no significant difference (P = 0.92), and the death hazard ratio was 0.98 (95% CI, 0.62-1.55). When the 106 patients with measurable or evaluable disease were considered, the objective response rate was 49% with TAM alone and 43% with TAM plus octreotide (P = 0.70). Patients who received TAM plus octreotide had higher incidences of nausea, diarrhea, and steatorrhea. The percentage of decline in serum IGF-I, from pretreatment levels to those following 3-6 weeks of treatment, was significantly greater (P < 0.01) with TAM plus octreotide than with TAM alone. CONCLUSIONS: There is no indication that the combination of TAM plus octreotide as administered in this study is substantially more efficacious than TAM alone in the treatment of postmenopausal women with metastatic breast carcinoma. The limited cohort included in IGF-I studies suggests that TAM plus octreotide produces a significantly greater reduction in serum IGF-I levels (Au). |
| Au: Bijker N; Rutgers EJ; Peterse JL; van Dongen JA; Hart AA; Borger JH; Kroon BB. ----- Ti: Low risk of locoregional recurrence of primary breast carcinoma after treatment with a modification of the Halsted radical mastectomy and selective use of radiotherapy. ----- So: Cancer. 85(8):1773-81, 1999 Apr 15. ----- Ab: BACKGROUND: The purpose of the current study was to evaluate the locoregional recurrence rate after treatment of patients with operable breast carcinoma with a modification of the Halsted radical mastectomy and the selective use of radiotherapy and to identify risk factors for locoregional recurrence. METHODS: Between 1979-1987, 691 consecutive patients underwent mastectomy after a negative biopsy of the axillary apical lymph nodes. The median age of the patients was 59 years (range, 26-89 years). The clinical tumor size was < 2 cm in 72 patients, 2-5 cm in 387 patients, and >5 cm in 169 patients; 16 patients had a T4 tumor. Surgery was comprised of a modification of the Halsted radical mastectomy, including at least part of the pectoralis major muscle and the entire pectoralis minor muscle, in 573 patients; 303 patients had positive axillary lymph nodes. Adjuvant radiotherapy to the chest wall and regional lymph nodes was given to 74 patients, whereas an additional 414 patients underwent irradiation to the internal mammary and medial supraclavicular lymph nodes. The median follow-up was 91 months. RESULTS: The actuarial overall survival rate was 82% at 5 years and 63% at 10 years. The 10-year chest wall and regional lymph node control rates, including patients with prior distant failures, were 95% and 94%, respectively. The only two significant prognostic factors for locoregional recurrence on multivariate analysis were lymph node status and pathologic tumor size. CONCLUSIONS: Excellent locoregional control can be achieved with a modified technique of radical mastectomy in patients with negative apical biopsy and the selective use of comprehensive radiotherapy. These results may serve as a reference outcome for comparison with other locoregional treatment strategies (Au). |
| Au: Makris A; Powles TJ; Kakolyris S; Dowsett M; Ashley SE; Harris AL. ----- Ti: Reduction in angiogenesis after neoadjuvant chemoendocrine therapy in patients with operable breast carcinoma. ----- So: Cancer. 85(9):1996-2000, 1999 May 1. ----- Ab: BACKGROUND: The intensity of angiogenesis, as measured by microvessel density, is a strong independent predictor of survival in breast carcinoma patients. The impact of chemotherapy and/or endocrine therapy on this process is unknown. METHODS: Histologic samples from patients randomized to a trial of neoadjuvant (NEO) versus adjuvant (ADJ) chemoendocrine therapy for operable breast carcinoma were obtained. Samples from 195 patients (90 NEO samples and 105 ADJ samples) were analyzed. Immunostaining was performed with the CD34 monoclonal antibody and the scoring of microvessels was performed using the Chalkley method. RESULTS: The median score of the NEO patients was 5.7 (95% confidence interval [CI], 5.3-6.0) and the median score of the ADJ patients was 6.3 (95% CI, 6-6.7) (P=0.025). Using previously validated scoring categories, there were fewer samples with a poor prognosis (score > or =7) in the NEO group (26%) compared with the ADJ group (32%) (P=0.04). CONCLUSIONS: The results of the current study suggest that NEO chemoendocrine therapy causes a reduction in microvessel density in primary breast carcinomas, which could be secondary to tumor regression or due to a direct effect on angiogenesis (Au). |
| Au: Macquart-Moulin G; Viens P; Genre D; Bouscary ML; Resbeut M; Gravis G; Camerlo J; Maraninchi D; Moatti JP. ----- Ti: Concomitant chemoradiotherapy for patients with nonmetastatic breast carcinoma: side effects, quality of life, and organization. ----- So: Cancer. 85(10):2190-9, 1999 May 15. ----- Ab: BACKGROUND: This study was designed to investigate the personal experience of patients with nonmetastatic breast carcinoma who were treated with the concurrent administration of radiotherapy and chemotherapy in terms of side effects and quality of life (QL). METHODS: One hundred nine patients with nonmetastatic breast carcinoma, recruited between May 1995 and February 1997, were included in a protocol combining chemotherapy with mitoxantrone and cyclophosphamide, administered intravenously in 4 cycles of 21 days, and concomitant radiotherapy. Side effects of treatment and its impact on patients' daily lives were measured using ad hoc questionnaires; QL was measured by the European Organization for Research and Treatment of Cancer QLQ-C30 QL questionnaire, and pain was measured by a visual analogue scale (VAS). RESULTS: All patients agreed to participate. The mean number of chemotherapy and radiotherapy symptoms per cycle were: 7.2+/-2.5 and 2.4+/-1.8, respectively. Chemotherapy symptoms generally were more frequent and distressing than those of radiotherapy. The average pain score reported on the VAS by patients during treatment was 3.0+/-2.0. Multidimensional QL assessment showed that treatment mainly affects physical functioning and global QL. Multivariate analysis showed that the main determinants of QL at the end of treatment were fatigue, pain, and loss of appetite experienced during treatment. Moreover, 62.8% of patients required specific help for transportation to the hospital and/or home upkeep. CONCLUSIONS: The concurrent administration of chemotherapy and radiotherapy deteriorates patients' QL but in a proportion similar to sequential administration while presenting the advantage of a shorter duration of treatment. However, increased fatigue, pain, and loss of appetite as well as difficulties in patients' daily lives have to be taken into account in therapeutic decision-making analysis (Au). |
| Au: Mankoff DA; Dunnwald LK; Gralow JR; Ellis GK; Drucker MJ; Livingston RB. ----- Ti: Monitoring the response of patients with locally advanced breast carcinoma to neoadjuvant chemotherapy using [technetium 99m]-sestamibi scintimammography. ----- So: Cancer. 85(11):2410-23, 1999 Jun 1. ----- Ab: BACKGROUND: Mammographic and physical examination assessments of the response of locally advanced breast carcinoma (LABC) to neoadjuvant therapy have been shown to be inaccurate. The authors studied the feasibility and accuracy of [technetium 99m]-sestamibi (MIBI) for monitoring the response of patients with LABC to neoadjuvant chemotherapy. METHODS: Patients receiving neoadjuvant chemotherapy for LABC underwent prone lateral scintimammography before therapy, after 2 months of therapy, and close to the completion of chemotherapy (presurgery) if chemotherapy continued for >3 months. Images were analyzed both qualitatively and quantitatively using the lesion-to-normal breast MIBI uptake ratio (L:N). Imaging results were compared with the clinical response and the pathologic response as determined from the posttherapy surgical specimen. RESULTS: A total of 32 patients (29 who were assessable for primary tumor response and 28 who were assessable for lymph node response) were included in the study. The mean change in the primary tumor L:N MIBI uptake ratio after 2 months of chemotherapy was -35% for clinical responders and +17% for nonresponders (P<0.001). Patients achieving a pathologic primary tumor macroscopic complete response (CR) had a mean change in uptake on the presurgical scan of -58% versus -18% for patients with a partial response (P<0.005). A decrease of > or =40% in the MIBI uptake ratio identified CRs with 100% sensitivity and 89% specificity. Pretherapy imaging predicted axillary lymph node metastases in 85% of patients ultimately found to have > or =1 positive lymph nodes at surgery, but was less accurate in identifying residual lymph node disease after therapy (55% sensitivity and 75% specificity). CONCLUSIONS: MIBI imaging accurately assessed the response to neoadjuvant chemotherapy in patients with LABC. Further studies are needed to determine the role of MIBI in this group of patients (Au). |
| Au: Hickok JT; Roscoe JA; Morrow GR; Stern RM; Yang B; Flynn PJ; Hynes HE; Kirshner JJ; Rosenbluth RJ. ----- Ti: Use of 5-HT3 receptor antagonists to prevent nausea and emesis caused by chemotherapy for patients with breast carcinoma in community practice settings. ----- So: Cancer. 86(1):64-71, 1999 Jul 1. ----- Ab: BACKGROUND: Although 5-HT3 receptor antagonists are clinically more effective in controlling emesis, particularly that caused by high dose cisplatin, than previously available agents, they appear to be less effective against nausea. This report focuses on the effectiveness of these agents against nausea and emesis in patients receiving two moderately emetogenic combination chemotherapy regimens as treatment for breast carcinoma in community practice settings. METHODS: Six hundred ninety-two breast carcinoma patients (688 female, 4 male; mean age, 51 years) enrolled in a nonrandomized study completed the Morrow Assessment of Nausea and Emesis (MANE) following 4 consecutive chemotherapy treatments. The frequency, duration, and severity of postchemotherapy nausea (PN) and postchemotherapy emesis (PE) were compared by type of antiemetic (5-HT3 receptor antagonist vs. other) and chemotherapy regimen (cyclophosphamide and doxorubicin with or without 5-fluorouracil [CA/CAF] vs. cyclophosphamide, methrotrexate, and 5-fluorouracil [CMF]). RESULTS: Within each regimen, the mean duration of PN was significantly longer for patients who received a 5-HT3 receptor antagonist than for those who were not given an antiemetic of that type (CA: 40.3 hours vs. 29.6 hours, P < 0.05; CMF: 37.6 hours vs. 30.2 hours, P < 0.05). There were no significant differences in the frequency or severity of nausea or in the frequency, severity, or duration of emesis by type of antiemetic for patients receiving either regimen. CONCLUSIONS: The results of this observational study suggest that 5-HT3 receptor antagonists are no more effective than other commonly used medications in controlling postchemotherapy nausea and emesis in women with breast carcinoma who are treated with moderately emetogenic chemotherapy in community practice settings. In fact, they may be associated with significant prolongation of the course of postchemotherapy nausea (Au). |
| Au: Nieder C. ----- Ti: Front-line chemotherapy with cisplatin and etoposide for patients with brain metastases from breast carcinoma, nonsmall cell lung carcinoma, or malignant melanoma. A prospective study [letter]. ----- So: Cancer. 86(5):900-3, 1999 Sep 1. |
| Au: Ibrahim NK; Rahman Z; Valero V; Willey J; Theriault RL; Buzdar AU; Murray JL 3rd; Bast R; Hortobagyi GN. ------ Ti: Phase II study of vinorelbine administered by 96-hour infusion in patients with advanced breast carcinoma. ----- So: Cancer. 86(7):1251-7, 1999 Oct 1. ----- Ab: BACKGROUND: Vinorelbine given by weekly bolus injection is active and less toxic than bolus vinblastine in the treatment of patients with metastatic breast carcinoma. Vinblastine given by 5-day continuous infusion showed a steep dose-response curve. Pharmacokinetic studies of vinorelbine showed that it is possible to achieve a comparable antitumor effect with a smaller amount of the drug if it is given by continuous infusion. The purpose of this study was to determine the efficacy of vinorelbine given by 96-hour continuous infusion to patients with refractory metastatic breast carcinoma patients. METHODS: Between May 1996 and August 1997, 47 patients with metastatic breast carcinoma were registered into the study. All patients previously had received doxorubicin and 70% had undergone prior paclitaxel treatment. Approximately 56% of the patients had >/=2 metastatic sites. All patients received vinorelbine according to the following dose schedule: 8 mg bolus followed by 11 mg/m(2) by continuous infusion over 24 hours every 4 days every 3 weeks. RESULTS: Forty-four patients were evaluable for response. A total of 193 cycles were administered. The overall response rate was 16% (2 patients achieved a complete response and 5 patients achieved a partial response). The median duration of response was 4.3 months and the median overall survival was 8.6 months. Patients with visceral metastases and/or multiple sites of involvement had shorter durations of response than patients with only soft tissue disease or single-site metastasis (3.1 months vs. 4. 9 months) and shorter overall survival (8.1 months vs. 12 months). Dose reductions were necessary due to cumulative stomatitis and/or fatigue in 12 cycles and neutropenia and/or infection in 13 cycles. CONCLUSIONS: Due to toxicity, a revised maximum tolerated dose for continuous infusion vinorelbine is proposed by the authors: 8 mg intravenously over 10 minutes followed by 10 mg/m(2) by continuous infusion over 24 hours every 4 days. The current dose schedule did not offer an advantage either in response rates or survival over the weekly vinorelbine bolus injection in doxorubicin-resistant and paclitaxel-resistant patients. Copyright 1999 American Cancer Society (Au). |
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