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Bernard Fisher - One of the best experts on this subject based on the ideXlab platform.
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five versus more than five years of Tamoxifen for lymph node negative breast cancer updated findings from the national surgical adjuvant breast and bowel project b 14 randomized trial
Journal of the National Cancer Institute, 2001Co-Authors: Bernard Fisher, James J Dignam, John Bryant, Norman WolmarkAbstract:Background: Previously reported information from B-14, a National Surgical Adjuvant Breast and Bowel Project (NSABP) randomized, placebo-controlled clinical trial, demonstrated that patients with estrogen receptor (ER)-positive breast cancer and negative axillary lymph nodes experienced a prolonged benefit from 5 years of Tamoxifen therapy. When these women were rerandomized to receive either placebo or more prolonged Tamoxifen therapy, they obtained no additional advantage from Tamoxifen through 4 years of follow-up. Because the optimal duration of Tamoxifen administration continues to be controversial and because there have been 3 more years of follow-up and a substantial increase in the number of events since our last report, an update of the B-14 study is appropriate. Methods: Patients (n = 1172) who had completed 5 years of Tamoxifen therapy and who were disease free were rerandomized to receive placebo (n = 579) or Tamoxifen (n = 593). Survival, disease-free survival (DFS), and relapse-free survival (RFS) were estimated by the Kaplan-Meier method; the differences between the treatment groups were assessed by the log-rank test. Relative risks of failure (with 95% confidence intervals) were determined by the Cox proportional hazards model. P values were two-sided. Results: Through 7 years after reassignment of Tamoxifen-treated patients to either placebo or continued Tamoxifen therapy, a slight advantage was observed in patients who discontinued Tamoxifen relative to those who continued to receive it: DFS = 82% versus 78% (P =.03), RFS = 94% versus 92% (P =.13), and survival = 94% versus 91% (P =.07), respectively. The lack of benefit from additional Tamoxifen therapy was independent of age or other characteristics. Conclusion: Through 7 years of follow-up after rerandomization, there continues to be no additional benefit from Tamoxifen administered beyond 5 years in women with ER-positive breast cancer and negative axillary lymph nodes.
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Tamoxifen and chemotherapy for lymph node negative estrogen receptor positive breast cancer
Journal of the National Cancer Institute, 1997Co-Authors: Bernard Fisher, James J Dignam, Birol Emir, John Bryant, Arthur Decillis, Norman Wolmark, Lawrence D Wickerham, Nikolay V Dimitrov, Neil Abramson, J N AtkinsAbstract:Background The B-20 study of the National Surgical Adjuvant Breast and Bowel Project (NSABP) was conducted to determine whether chemotherapy plus Tamoxifen would be of greater benefit than Tamoxifen alone in the treatment of patients with axillary lymph node-negative, estrogen receptor-positive breast cancer. Methods Eligible patients (n = 2306) were randomly assigned to one of three treatment groups following surgery. A total of 771 patients with follow-up data received Tamoxifen alone; 767 received methotrexate, fluorouracil, and Tamoxifen (MFT); and 768 received cyclophosphamide, methotrexate, fluorouracil, and Tamoxifen (CMFT). The Kaplan-Meier method was used to estimate disease-free survival, distant disease-free survival, and survival. Reported P values are two-sided. Results Through 5 years of follow-up, chemotherapy plus Tamoxifen resulted in significantly better disease-free survival than Tamoxifen alone (90% for MFT versus 85% for Tamoxifen [P = .01]; 89% for CMFT versus 85% for Tamoxifen [P = .001]). A similar benefit was observed in both distant disease-free survival (92% for MFT versus 87% for Tamoxifen [P = .008]; 91% for CMFT versus 87% for Tamoxifen [P = .006]) and survival (97% for MFT versus 94% for Tamoxifen [P = .05]; 96% for CMFT versus 94% for Tamoxifen [P = .03]). Compared with Tamoxifen alone, MFT and CMFT reduced the risk of ipsilateral breast tumor recurrence after lumpectomy and the risk of recurrence at other local, regional, and distant sites. Risk of treatment failure was reduced after both types of chemotherapy, regardless of tumor size, tumor estrogen or progesterone receptor level, or patient age; however, the reduction was greatest in patients aged 49 years or less. No subgroup of patients evaluated in this study failed to benefit from chemotherapy. Conclusions Findings from this and other NSABP studies indicate that patients with breast cancer who meet NSABP protocol criteria, regardless of age, lymph node status, tumor size, or estrogen receptor status, are candidates for chemotherapy.
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five versus more than five years of Tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor positive tumors
Journal of the National Cancer Institute, 1996Co-Authors: Bernard Fisher, James J Dignam, John Bryant, Arthur Decillis, Norman Wolmark, Lawrence D Wickerham, Joseph P Costantino, C Redmond, Edwin R Fisher, D BowmanAbstract:BACKGROUND: In 1982, the National Surgical Adjuvant Breast and Bowel Project initiated a randomized, double-blinded, placebo-controlled trial (B-14) to determine the effectiveness of adjuvant Tamoxifen therapy in patients with primary operable breast cancer who had estrogen receptor-positive tumors and no axillary lymph node involvement. The findings indicated that Tamoxifen therapy provided substantial benefit to patients with early stage disease. However, questions arose about how long the observed benefit would persist, about the duration of therapy necessary to maintain maximum benefit, and about the nature and severity of adverse effects from prolonged treatment. PURPOSE: We evaluated the outcome of patients in the B-14 trial through 10 years of follow-up. In addition, the effects of 5 years versus more than 5 years of Tamoxifen therapy were compared. METHODS: In the trial, patients were initially assigned to receive either Tamoxifen at 20 mg/day (n = 1404) or placebo (n = 1414). Tamoxifen-treated patients who remained disease free after 5 years of therapy were then reassigned to receive either another 5 years of Tamoxifen (n = 322) or 5 years of placebo (n = 321). After the study began, another group of patients who met the same protocol eligibility requirements as the randomly assigned patients were registered to receive Tamoxifen (n = 1211). Registered patients who were disease free after 5 years of treatment were also randomly assigned to another 5 years of Tamoxifen (n = 261) or to 5 years of placebo (n = 249). To compare 5 years with more than 5 years of Tamoxifen therapy, data relating to all patients reassigned to an additional 5 years of the drug were combined. Patients who were not reassigned to either Tamoxifen or placebo continued to be followed in the study. Survival, disease-free survival, and distant disease-free survival (relating to failure at distant sites) were estimated by use of the Kaplan-Meier method; differences between the treatment groups were assessed by use of the logrank test. The relative risks of failure (with 95% confidence intervals [CIs]) were determined by use of the Cox proportional hazards model. Reported P values are two-sided. RESULTS: Through 10 years of follow-up, a significant advantage in disease-free survival (69% versus 57%, P < .0001; relative risk = 0.66; 95% CI = 0.58-0.74), distant disease-free survival (76% versus 67%, P < .0001; relative risk = 0.70; 95% CI = 0.61-0.81), and survival (80% versus 76%, P = .02; relative risk = 0.84; 95% CI = 0.71-0.99) was found for patients in the group first assigned to receive Tamoxifen. The survival benefit extended to those 49 years of age or younger and to those 50 years of age or older. Tamoxifen therapy was associated with a 37% reduction in the incidence of contralateral (opposite) breast cancer (P = .007). Through 4 years after the reassignment of Tamoxifen-treated patients to either continued-therapy or placebo groups, advantages in disease-free survival (92% versus 86%, P = .003) and distant disease-free survival (96% versus 90%, P = .01) were found for those who discontinued Tamoxifen treatment. Survival was 96% for those who discontinued Tamoxifen compared with 94% for those who continued Tamoxifen treatment (P = .08). A higher incidence of thromboembolic events was seen in Tamoxifen-treated patients (through 5 years, 1.7% versus 0.4%). Except for endometrial cancer, the incidence of second cancers was not increased with Tamoxifen therapy. CONCLUSIONS AND IMPLICATIONS: The benefit from 5 years of Tamoxifen therapy persists through 10 years of follow-up. No additional advantage is obtained from continuing Tamoxifen therapy for more than 5 years.
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endometrial cancer in Tamoxifen treated breast cancer patients findings from the national surgical adjuvant breast and bowel project nsabp b 14
Journal of the National Cancer Institute, 1994Co-Authors: Bernard Fisher, Joseph P Costantino, C Redmond, Edwin R Fisher, D L Wickerham, Walter M CroninAbstract:BACKGROUND Tamoxifen is advantageous in treating all stages of breast cancer. However, studies have suggested that incidence and severity of endometrial cancer increase in women treated with Tamoxifen. PURPOSE We compared rates of endometrial and other cancers in Tamoxifen- and non-Tamoxifen-treated patients and described the pathologic characteristics of the endometrial cancers. METHODS Data were analyzed on 2843 patients with node-negative, estrogen receptor-positive, invasive breast cancer randomly assigned to placebo or Tamoxifen (20 mg/d) and on 1220 Tamoxifen-treated patients registered in NSABP B-14 subsequent to randomization. Average time on study is 8 years for randomly assigned patients and 5 years for registered patients. RESULTS The incidence rates of liver, gastrointestinal, urinary tract, and nonuterine genital tumors were not increased by Tamoxifen treatment. Twenty-five endometrial cancers were originally reported, one of which was reclassified after subsequent review. Two cases occurred in the placebo group in patients whose medical status subsequent to random assignment had required Tamoxifen treatment. Twenty-three occurred in the Tamoxifen groups. Twenty-one of the 24 originally reported endometrial cancers were FIGO stage 1; 18 of 23 gradable cases were of good to moderate histologic grade. Four Tamoxifen-treated women died of uterine cancer. The average annual hazard rate of endometrial cancer as a first event within the first 5 years of follow-up in the randomized, Tamoxifen-treated group was 1.2/1000 patient-years; the cumulative hazard rate was 6.3/1000. Findings for the registered, Tamoxifen-treated group were similar. Including all originally reported endometrial cancers, the annual hazard rate through all follow-up was 0.2/1000 in the placebo group and 1.6/1000 in the randomized, Tamoxifen-treated group; the relative risk of endometrial cancer for the latter versus the former group was 7.5. Again for the latter group, using population-based rates of endometrial cancer from SEER data and information from another NSABP (B-06) trial, relative risks were 2.2 and 2.3, respectively. The 5-year cumulative hazard rate for disease-free survival in the randomized Tamoxifen group was 38% less than that in the placebo group. Some data in this paper were provided by an investigator who submitted fraudulent data to the NSABP [see the "News" section]; therefore, the reader must read the entire text including Table 10 and the Editor's notes. In brief, data on 182 of the 2843 randomly assigned patients and 37 of the 1220 registered patients were provided by the investigator in question. After review, 24 of the 182 records showed falsification, all involving characteristics of patients prior to random assignment. Of the 37 registered-patient records, 8 showed falsification. CONCLUSIONS Risk of endometrial cancer increases following Tamoxifen therapy for invasive breast cancer; however, net benefit greatly outweighs risk. Endometrial cancers occurring after Tamoxifen therapy do not appear to be of a different type with a worse prognosis than are such tumors in non-Tamoxifen-treated patients. IMPLICATIONS Tamoxifen treatment for breast cancer should continue. In addition, the relative risk of endometrial cancer observed in B-14 Tamoxifen-treated patients is consistent with the twofold relative risk used in the initial risk-benefit computation for the NSABP breast cancer prevention trial.
John Bryant - One of the best experts on this subject based on the ideXlab platform.
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five versus more than five years of Tamoxifen for lymph node negative breast cancer updated findings from the national surgical adjuvant breast and bowel project b 14 randomized trial
Journal of the National Cancer Institute, 2001Co-Authors: Bernard Fisher, James J Dignam, John Bryant, Norman WolmarkAbstract:Background: Previously reported information from B-14, a National Surgical Adjuvant Breast and Bowel Project (NSABP) randomized, placebo-controlled clinical trial, demonstrated that patients with estrogen receptor (ER)-positive breast cancer and negative axillary lymph nodes experienced a prolonged benefit from 5 years of Tamoxifen therapy. When these women were rerandomized to receive either placebo or more prolonged Tamoxifen therapy, they obtained no additional advantage from Tamoxifen through 4 years of follow-up. Because the optimal duration of Tamoxifen administration continues to be controversial and because there have been 3 more years of follow-up and a substantial increase in the number of events since our last report, an update of the B-14 study is appropriate. Methods: Patients (n = 1172) who had completed 5 years of Tamoxifen therapy and who were disease free were rerandomized to receive placebo (n = 579) or Tamoxifen (n = 593). Survival, disease-free survival (DFS), and relapse-free survival (RFS) were estimated by the Kaplan-Meier method; the differences between the treatment groups were assessed by the log-rank test. Relative risks of failure (with 95% confidence intervals) were determined by the Cox proportional hazards model. P values were two-sided. Results: Through 7 years after reassignment of Tamoxifen-treated patients to either placebo or continued Tamoxifen therapy, a slight advantage was observed in patients who discontinued Tamoxifen relative to those who continued to receive it: DFS = 82% versus 78% (P =.03), RFS = 94% versus 92% (P =.13), and survival = 94% versus 91% (P =.07), respectively. The lack of benefit from additional Tamoxifen therapy was independent of age or other characteristics. Conclusion: Through 7 years of follow-up after rerandomization, there continues to be no additional benefit from Tamoxifen administered beyond 5 years in women with ER-positive breast cancer and negative axillary lymph nodes.
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weighing the risks and benefits of Tamoxifen treatment for preventing breast cancer
Journal of the National Cancer Institute, 1999Co-Authors: Mitchell H Gail, John Bryant, Joseph P Costantino, Robert T Croyle, Laurence S Freedman, Kathy J Helzlsouer, Victor G VogelAbstract:Background In response to findings from the Breast Cancer Prevention Trial that Tamoxifen treatment produced a 49% reduction in the risk of invasive breast cancer in a population of women at elevated risk, the National Cancer Institute sponsored a workshop on July 7 and 8, 1998, to develop information to assist in counseling and in weighing the risks and benefits of Tamoxifen. Our study was undertaken to develop tools to identify women for whom the benefits outweigh the risks. Methods Information was reviewed on the incidence of invasive breast cancer and of in situ lesions, as well as on several other health outcomes, in the absence of Tamoxifen treatment. Data on the effects of Tamoxifen on these outcomes were also reviewed, and methods were developed to compare the risks and benefits of Tamoxifen. Results The risks and benefits of Tamoxifen depend on age and race, as well as on a woman's specific risk factors for breast cancer. In particular, the absolute risks from Tamoxifen of endometrial cancer, stroke, pulmonary embolism, and deep vein thrombosis increase with age, and these absolute risks differ between white and black women, as does the protective effect of Tamoxifen on fractures. Tables and aids are developed to describe the risks and benefits of Tamoxifen and to identify classes of women for whom the benefits outweigh the risks. Conclusions Tamoxifen is most beneficial for younger women with an elevated risk of breast cancer. The quantitative analyses presented can assist health care providers and women in weighing the risks and benefits of Tamoxifen for reducing breast cancer risk.
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Tamoxifen and chemotherapy for lymph node negative estrogen receptor positive breast cancer
Journal of the National Cancer Institute, 1997Co-Authors: Bernard Fisher, James J Dignam, Birol Emir, John Bryant, Arthur Decillis, Norman Wolmark, Lawrence D Wickerham, Nikolay V Dimitrov, Neil Abramson, J N AtkinsAbstract:Background The B-20 study of the National Surgical Adjuvant Breast and Bowel Project (NSABP) was conducted to determine whether chemotherapy plus Tamoxifen would be of greater benefit than Tamoxifen alone in the treatment of patients with axillary lymph node-negative, estrogen receptor-positive breast cancer. Methods Eligible patients (n = 2306) were randomly assigned to one of three treatment groups following surgery. A total of 771 patients with follow-up data received Tamoxifen alone; 767 received methotrexate, fluorouracil, and Tamoxifen (MFT); and 768 received cyclophosphamide, methotrexate, fluorouracil, and Tamoxifen (CMFT). The Kaplan-Meier method was used to estimate disease-free survival, distant disease-free survival, and survival. Reported P values are two-sided. Results Through 5 years of follow-up, chemotherapy plus Tamoxifen resulted in significantly better disease-free survival than Tamoxifen alone (90% for MFT versus 85% for Tamoxifen [P = .01]; 89% for CMFT versus 85% for Tamoxifen [P = .001]). A similar benefit was observed in both distant disease-free survival (92% for MFT versus 87% for Tamoxifen [P = .008]; 91% for CMFT versus 87% for Tamoxifen [P = .006]) and survival (97% for MFT versus 94% for Tamoxifen [P = .05]; 96% for CMFT versus 94% for Tamoxifen [P = .03]). Compared with Tamoxifen alone, MFT and CMFT reduced the risk of ipsilateral breast tumor recurrence after lumpectomy and the risk of recurrence at other local, regional, and distant sites. Risk of treatment failure was reduced after both types of chemotherapy, regardless of tumor size, tumor estrogen or progesterone receptor level, or patient age; however, the reduction was greatest in patients aged 49 years or less. No subgroup of patients evaluated in this study failed to benefit from chemotherapy. Conclusions Findings from this and other NSABP studies indicate that patients with breast cancer who meet NSABP protocol criteria, regardless of age, lymph node status, tumor size, or estrogen receptor status, are candidates for chemotherapy.
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five versus more than five years of Tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor positive tumors
Journal of the National Cancer Institute, 1996Co-Authors: Bernard Fisher, James J Dignam, John Bryant, Arthur Decillis, Norman Wolmark, Lawrence D Wickerham, Joseph P Costantino, C Redmond, Edwin R Fisher, D BowmanAbstract:BACKGROUND: In 1982, the National Surgical Adjuvant Breast and Bowel Project initiated a randomized, double-blinded, placebo-controlled trial (B-14) to determine the effectiveness of adjuvant Tamoxifen therapy in patients with primary operable breast cancer who had estrogen receptor-positive tumors and no axillary lymph node involvement. The findings indicated that Tamoxifen therapy provided substantial benefit to patients with early stage disease. However, questions arose about how long the observed benefit would persist, about the duration of therapy necessary to maintain maximum benefit, and about the nature and severity of adverse effects from prolonged treatment. PURPOSE: We evaluated the outcome of patients in the B-14 trial through 10 years of follow-up. In addition, the effects of 5 years versus more than 5 years of Tamoxifen therapy were compared. METHODS: In the trial, patients were initially assigned to receive either Tamoxifen at 20 mg/day (n = 1404) or placebo (n = 1414). Tamoxifen-treated patients who remained disease free after 5 years of therapy were then reassigned to receive either another 5 years of Tamoxifen (n = 322) or 5 years of placebo (n = 321). After the study began, another group of patients who met the same protocol eligibility requirements as the randomly assigned patients were registered to receive Tamoxifen (n = 1211). Registered patients who were disease free after 5 years of treatment were also randomly assigned to another 5 years of Tamoxifen (n = 261) or to 5 years of placebo (n = 249). To compare 5 years with more than 5 years of Tamoxifen therapy, data relating to all patients reassigned to an additional 5 years of the drug were combined. Patients who were not reassigned to either Tamoxifen or placebo continued to be followed in the study. Survival, disease-free survival, and distant disease-free survival (relating to failure at distant sites) were estimated by use of the Kaplan-Meier method; differences between the treatment groups were assessed by use of the logrank test. The relative risks of failure (with 95% confidence intervals [CIs]) were determined by use of the Cox proportional hazards model. Reported P values are two-sided. RESULTS: Through 10 years of follow-up, a significant advantage in disease-free survival (69% versus 57%, P < .0001; relative risk = 0.66; 95% CI = 0.58-0.74), distant disease-free survival (76% versus 67%, P < .0001; relative risk = 0.70; 95% CI = 0.61-0.81), and survival (80% versus 76%, P = .02; relative risk = 0.84; 95% CI = 0.71-0.99) was found for patients in the group first assigned to receive Tamoxifen. The survival benefit extended to those 49 years of age or younger and to those 50 years of age or older. Tamoxifen therapy was associated with a 37% reduction in the incidence of contralateral (opposite) breast cancer (P = .007). Through 4 years after the reassignment of Tamoxifen-treated patients to either continued-therapy or placebo groups, advantages in disease-free survival (92% versus 86%, P = .003) and distant disease-free survival (96% versus 90%, P = .01) were found for those who discontinued Tamoxifen treatment. Survival was 96% for those who discontinued Tamoxifen compared with 94% for those who continued Tamoxifen treatment (P = .08). A higher incidence of thromboembolic events was seen in Tamoxifen-treated patients (through 5 years, 1.7% versus 0.4%). Except for endometrial cancer, the incidence of second cancers was not increased with Tamoxifen therapy. CONCLUSIONS AND IMPLICATIONS: The benefit from 5 years of Tamoxifen therapy persists through 10 years of follow-up. No additional advantage is obtained from continuing Tamoxifen therapy for more than 5 years.
Jack Cuzick - One of the best experts on this subject based on the ideXlab platform.
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factors predicting late recurrence for estrogen receptor positive breast cancer
Journal of the National Cancer Institute, 2013Co-Authors: Ivana Sestak, Mitch Dowsett, Lila Zabaglo, Elena Lopezknowles, Sean Ferree, Wayne J Cowens, Jack CuzickAbstract:Adjuvant chemotherapy and endocrine therapy for early breast cancer have had a considerable impact on outcomes (1), but a substantial number of women, especially those with estrogen receptor (ER)–positive tumors, remain at risk for late recurrences. The annual rate is in excess of 2% for at least 15 years, even after 5 years of Tamoxifen therapy (2), and currently it is not possible to identify a group of such women who can be considered as cured (3,4). This remains true for at least 10 years for women treated for 5 years with an aromatase inhibitor (5). Most of the studies of prevention of late relapse have been performed in women receiving Tamoxifen as initial adjuvant endocrine therapy for early ER-positive breast cancer. The MA17 trial clearly showed that extended adjuvant therapy with letrozole after 5 years of Tamoxifen prolongs disease-free survival and overall survival, regardless of the patient’s nodal status involvement (6). Brewster et al. (7) found that ER positivity, nodal involvement, and grade were all associated with increased risk of late recurrence. It is of importance to determine to what extent the newer immunohistochemical and molecular scores can help in predicting late recurrence. Recent publications from the transATAC (Anastrozole, Tamozifen, Alone or in Combination) cohort have demonstrated that the Oncotype DX recurrence score (RS) (8), the immunohistochemical (IHC4) score (9) and the PAM50-based risk of recurrence (ROR) score (10) all provide additional information beyond that available for clinical variables, summarized in the clinical treatment score (CTS), about the risk of distant recurrence in postmenopausal women with hormone receptor–positive breast cancer treated with anastrozole or Tamoxifen, but it is unknown how much of this effect extends beyond 5 years. Here, we investigate the relationship between clinical variables, immunohistochemical markers, and these scores for the prediction of distant recurrence separately in years 0 to 5 and years 5 to 10 after diagnosis for postmenopausal women with early hormone receptor–positive breast cancer.
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pharmacokinetics of anastrozole and Tamoxifen alone and in combination during adjuvant endocrine therapy for early breast cancer in postmenopausal women a sub protocol of the arimidex and Tamoxifen alone or in combination atac trial
British Journal of Cancer, 2001Co-Authors: Mitch Dowsett, Jack Cuzick, Anthony Howell, I JacksonAbstract:The ATAC trial evaluates in a randomized, double-blind design, Arimdex(TM) (anastrozole) alone or in combination with Tamoxifen, relative to Tamoxifen alone as 5-year adjuvant treatment in postmenopausal women with early breast cancer. Patients included in the pharmacokinetic (PK) sub-protocol had been in ATAC for greater than or equal to3 months, taking their medication in the morning and were 100% compliant for the preceding 14 days. Blood samples were collected 24 +/- 4 h after last dose. Trough (C-min) plasma concentrations of anastrozole, Tamoxifen and desmethylTamoxifen (DMT) were measured by validated methods. The PK results were based on a total of 347 patients (131 anastrozole (1 mg o.d.), 111 Tamoxifen (20 mg o.d.), 105 anastrozole and Tamoxifen (1 and 20 mg o.d. respectively)). The geometric mean steady-state trough plasma concentrations of Tamoxifen and DMT were statistically equivalent in patients receiving Tamoxifen alone or in combination with anastrozole: geometric mean Tamoxifen = 94.8 ng ml(-1) and 95.3 ng ml(-1) in Tamoxifen alone and combination groups, respectively; geometric mean DMT = 265.1 and 277.6 ng ml(-1) in the Tamoxifen and anastrozole and Tamoxifen groups, respectively. The geometric mean anastrozole levels were 27% lower (90% Cl 20-33%; P < 0.001) in the presence of Tamoxifen than with anastrozole alone. Baseline plasma oestradiol levels were not obtained in the PK sub-protocol, however, such information was available from a similar ATAC sub-protocol, which evaluated bone mineral density. Mean oestradiol levels were 21.3, 19.3, and 21.6 pmol l(-1) prior to treatment and 3.7, 20.9 and 3.6 pmol l(-1) after 3 months in the anastrozole, Tamoxifen, and combination groups, respectively (n = 167). On- treatment values were below the detection limit (3 pmol l(-1)) in 43.6 and 38.5% of the anastrozole alone and anastrozole in combination with Tamoxifen groups, respectively. As a result of (a) the lack of effect of anastrozole on Tamoxifen and DMT levels and (b) the observed fall in blood anastrozole levels having no significant effect on oestradiol suppression by anastrozole, we conclude that the observed reduction in anastrozole levels by Tamoxifen is unlikely to be of clinical significance when anastrozole and Tamoxifen are administered together. (C) 2001 Cancer Research Campaign
Norman Wolmark - One of the best experts on this subject based on the ideXlab platform.
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five versus more than five years of Tamoxifen for lymph node negative breast cancer updated findings from the national surgical adjuvant breast and bowel project b 14 randomized trial
Journal of the National Cancer Institute, 2001Co-Authors: Bernard Fisher, James J Dignam, John Bryant, Norman WolmarkAbstract:Background: Previously reported information from B-14, a National Surgical Adjuvant Breast and Bowel Project (NSABP) randomized, placebo-controlled clinical trial, demonstrated that patients with estrogen receptor (ER)-positive breast cancer and negative axillary lymph nodes experienced a prolonged benefit from 5 years of Tamoxifen therapy. When these women were rerandomized to receive either placebo or more prolonged Tamoxifen therapy, they obtained no additional advantage from Tamoxifen through 4 years of follow-up. Because the optimal duration of Tamoxifen administration continues to be controversial and because there have been 3 more years of follow-up and a substantial increase in the number of events since our last report, an update of the B-14 study is appropriate. Methods: Patients (n = 1172) who had completed 5 years of Tamoxifen therapy and who were disease free were rerandomized to receive placebo (n = 579) or Tamoxifen (n = 593). Survival, disease-free survival (DFS), and relapse-free survival (RFS) were estimated by the Kaplan-Meier method; the differences between the treatment groups were assessed by the log-rank test. Relative risks of failure (with 95% confidence intervals) were determined by the Cox proportional hazards model. P values were two-sided. Results: Through 7 years after reassignment of Tamoxifen-treated patients to either placebo or continued Tamoxifen therapy, a slight advantage was observed in patients who discontinued Tamoxifen relative to those who continued to receive it: DFS = 82% versus 78% (P =.03), RFS = 94% versus 92% (P =.13), and survival = 94% versus 91% (P =.07), respectively. The lack of benefit from additional Tamoxifen therapy was independent of age or other characteristics. Conclusion: Through 7 years of follow-up after rerandomization, there continues to be no additional benefit from Tamoxifen administered beyond 5 years in women with ER-positive breast cancer and negative axillary lymph nodes.
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Tamoxifen and chemotherapy for lymph node negative estrogen receptor positive breast cancer
Journal of the National Cancer Institute, 1997Co-Authors: Bernard Fisher, James J Dignam, Birol Emir, John Bryant, Arthur Decillis, Norman Wolmark, Lawrence D Wickerham, Nikolay V Dimitrov, Neil Abramson, J N AtkinsAbstract:Background The B-20 study of the National Surgical Adjuvant Breast and Bowel Project (NSABP) was conducted to determine whether chemotherapy plus Tamoxifen would be of greater benefit than Tamoxifen alone in the treatment of patients with axillary lymph node-negative, estrogen receptor-positive breast cancer. Methods Eligible patients (n = 2306) were randomly assigned to one of three treatment groups following surgery. A total of 771 patients with follow-up data received Tamoxifen alone; 767 received methotrexate, fluorouracil, and Tamoxifen (MFT); and 768 received cyclophosphamide, methotrexate, fluorouracil, and Tamoxifen (CMFT). The Kaplan-Meier method was used to estimate disease-free survival, distant disease-free survival, and survival. Reported P values are two-sided. Results Through 5 years of follow-up, chemotherapy plus Tamoxifen resulted in significantly better disease-free survival than Tamoxifen alone (90% for MFT versus 85% for Tamoxifen [P = .01]; 89% for CMFT versus 85% for Tamoxifen [P = .001]). A similar benefit was observed in both distant disease-free survival (92% for MFT versus 87% for Tamoxifen [P = .008]; 91% for CMFT versus 87% for Tamoxifen [P = .006]) and survival (97% for MFT versus 94% for Tamoxifen [P = .05]; 96% for CMFT versus 94% for Tamoxifen [P = .03]). Compared with Tamoxifen alone, MFT and CMFT reduced the risk of ipsilateral breast tumor recurrence after lumpectomy and the risk of recurrence at other local, regional, and distant sites. Risk of treatment failure was reduced after both types of chemotherapy, regardless of tumor size, tumor estrogen or progesterone receptor level, or patient age; however, the reduction was greatest in patients aged 49 years or less. No subgroup of patients evaluated in this study failed to benefit from chemotherapy. Conclusions Findings from this and other NSABP studies indicate that patients with breast cancer who meet NSABP protocol criteria, regardless of age, lymph node status, tumor size, or estrogen receptor status, are candidates for chemotherapy.
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five versus more than five years of Tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor positive tumors
Journal of the National Cancer Institute, 1996Co-Authors: Bernard Fisher, James J Dignam, John Bryant, Arthur Decillis, Norman Wolmark, Lawrence D Wickerham, Joseph P Costantino, C Redmond, Edwin R Fisher, D BowmanAbstract:BACKGROUND: In 1982, the National Surgical Adjuvant Breast and Bowel Project initiated a randomized, double-blinded, placebo-controlled trial (B-14) to determine the effectiveness of adjuvant Tamoxifen therapy in patients with primary operable breast cancer who had estrogen receptor-positive tumors and no axillary lymph node involvement. The findings indicated that Tamoxifen therapy provided substantial benefit to patients with early stage disease. However, questions arose about how long the observed benefit would persist, about the duration of therapy necessary to maintain maximum benefit, and about the nature and severity of adverse effects from prolonged treatment. PURPOSE: We evaluated the outcome of patients in the B-14 trial through 10 years of follow-up. In addition, the effects of 5 years versus more than 5 years of Tamoxifen therapy were compared. METHODS: In the trial, patients were initially assigned to receive either Tamoxifen at 20 mg/day (n = 1404) or placebo (n = 1414). Tamoxifen-treated patients who remained disease free after 5 years of therapy were then reassigned to receive either another 5 years of Tamoxifen (n = 322) or 5 years of placebo (n = 321). After the study began, another group of patients who met the same protocol eligibility requirements as the randomly assigned patients were registered to receive Tamoxifen (n = 1211). Registered patients who were disease free after 5 years of treatment were also randomly assigned to another 5 years of Tamoxifen (n = 261) or to 5 years of placebo (n = 249). To compare 5 years with more than 5 years of Tamoxifen therapy, data relating to all patients reassigned to an additional 5 years of the drug were combined. Patients who were not reassigned to either Tamoxifen or placebo continued to be followed in the study. Survival, disease-free survival, and distant disease-free survival (relating to failure at distant sites) were estimated by use of the Kaplan-Meier method; differences between the treatment groups were assessed by use of the logrank test. The relative risks of failure (with 95% confidence intervals [CIs]) were determined by use of the Cox proportional hazards model. Reported P values are two-sided. RESULTS: Through 10 years of follow-up, a significant advantage in disease-free survival (69% versus 57%, P < .0001; relative risk = 0.66; 95% CI = 0.58-0.74), distant disease-free survival (76% versus 67%, P < .0001; relative risk = 0.70; 95% CI = 0.61-0.81), and survival (80% versus 76%, P = .02; relative risk = 0.84; 95% CI = 0.71-0.99) was found for patients in the group first assigned to receive Tamoxifen. The survival benefit extended to those 49 years of age or younger and to those 50 years of age or older. Tamoxifen therapy was associated with a 37% reduction in the incidence of contralateral (opposite) breast cancer (P = .007). Through 4 years after the reassignment of Tamoxifen-treated patients to either continued-therapy or placebo groups, advantages in disease-free survival (92% versus 86%, P = .003) and distant disease-free survival (96% versus 90%, P = .01) were found for those who discontinued Tamoxifen treatment. Survival was 96% for those who discontinued Tamoxifen compared with 94% for those who continued Tamoxifen treatment (P = .08). A higher incidence of thromboembolic events was seen in Tamoxifen-treated patients (through 5 years, 1.7% versus 0.4%). Except for endometrial cancer, the incidence of second cancers was not increased with Tamoxifen therapy. CONCLUSIONS AND IMPLICATIONS: The benefit from 5 years of Tamoxifen therapy persists through 10 years of follow-up. No additional advantage is obtained from continuing Tamoxifen therapy for more than 5 years.
Prudence A Francis - One of the best experts on this subject based on the ideXlab platform.
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tailoring adjuvant endocrine therapy for premenopausal breast cancer
The New England Journal of Medicine, 2018Co-Authors: Marco Colleoni, Prudence A Francis, Istvan Lang, Olivia Pagani, Gini F Fleming, Barbara Walley, Henry L Gomez, Carlo Tondini, Eva CiruelosAbstract:Abstract Background In the Suppression of Ovarian Function Trial (SOFT) and the Tamoxifen and Exemestane Trial (TEXT), the 5-year rates of recurrence of breast cancer were significantly lower among premenopausal women who received the aromatase inhibitor exemestane plus ovarian suppression than among those who received Tamoxifen plus ovarian suppression. The addition of ovarian suppression to Tamoxifen did not result in significantly lower recurrence rates than those with Tamoxifen alone. Here, we report the updated results from the two trials. Methods Premenopausal women were randomly assigned to receive 5 years of Tamoxifen, Tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression in SOFT and to receive Tamoxifen plus ovarian suppression or exemestane plus ovarian suppression in TEXT. Randomization was stratified according to the receipt of chemotherapy. Results In SOFT, the 8-year disease-free survival rate was 78.9% with Tamoxifen alone, 83.2% with Tamoxifen plus ovarian suppression,...
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adjuvant ovarian suppression in premenopausal breast cancer
The New England Journal of Medicine, 2015Co-Authors: Meredith M. Regan, Prudence A Francis, Istvan Lang, Eva Ciruelos, Gini F Fleming, Meritxell Bellet, Herve Bonnefoi, Miguel Angel Climent, Gian Antonio Da PradaAbstract:We randomly assigned 3066 premenopausal women, stratified according to prior receipt or nonreceipt of chemotherapy, to receive 5 years of Tamoxifen, Tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression. The primary analysis tested the hypothesis that Tamoxifen plus ovarian suppression would improve disease-free survival, as compared with Tamoxifen alone. In the primary analysis, 46.7% of the patients had not received chemotherapy previously, and 53.3% had received chemotherapy and remained premenopausal. RESULTS After a median follow-up of 67 months, the estimated disease-free survival rate at 5 years was 86.6% in the Tamoxifen–ovarian suppression group and 84.7% in the Tamoxifen group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.83; 95% confidence interval [CI], 0.66 to 1.04; P = 0.10). Multivariable allowance for prognostic factors suggested a greater treatment effect with Tamoxifen plus ovarian suppression than with Tamoxifen alone (hazard ratio, 0.78; 95% CI, 0.62 to 0.98). Most recurrences occurred in patients who had received prior chemotherapy, among whom the rate of freedom from breast cancer at 5 years was 82.5% in the Tamoxifen–ovarian suppression group and 78.0% in the Tamoxifen group (hazard ratio for recurrence, 0.78; 95% CI, 0.60 to 1.02). At 5 years, the rate of freedom from breast cancer was 85.7% in the exemestane–ovarian suppression group (hazard ratio for recurrence vs. Tamoxifen, 0.65; 95% CI, 0.49 to 0.87). CONCLUSIONS Adding ovarian suppression to Tamoxifen did not provide a significant benefit in the overall study population. However, for women who were at sufficient risk for recurrence to warrant adjuvant chemotherapy and who remained premenopausal, the addition of ovarian suppression improved disease outcomes. Further improvement was seen with the use of exemestane plus ovarian suppression. (Funded by Pfizer and others; SOFT ClinicalTrials.gov number, NCT00066690.)