Showing papers by "Bernard Fisher published in 1989"
TL;DR: The observations through eight years are consistent with the findings at five years and that these new findings continue to support the use of lumpectomy in patients with Stage I or II breast cancer, and it is concluded that irradiation reduces the probability of local recurrence of tumor in patients treated with Lumpectomy.
Abstract: In 1985 we presented results of a randomized trial involving 1843 women followed for five years that indicated that segmental breast resection (lumpectomy) followed by breast irradiation is appropriate therapy for patients with Stage I or II breast cancer (tumor size, less than or equal to 4 cm), provided that the margins of the resected specimens are free of tumor. Women with positive axillary nodes received adjuvant chemotherapy. Lumpectomy followed by irradiation resulted in a five-year survival rate of 85 percent, as compared with 76 percent for total mastectomy, a rate of survival free of distant disease of 76 percent, as compared with 72 percent, and a disease-free survival rate of 72 percent, as compared with 66 percent. In the current study, we have extended our observations through eight years of follow-up. Ninety percent of the women treated with breast irradiation after lumpectomy remained free of ipsilateral breast tumor, as compared with 61 percent of those not treated with irradiation after lumpectomy (P less than 0.001). Among patients with positive axillary nodes, only 6 percent of those treated with radiation and adjuvant chemotherapy had a recurrence of tumor in the ipsilateral breast. Lumpectomy with or without irradiation of the breast resulted in rates of disease-free survival (58 +/- 2.6 percent), distant-disease-free survival (65 +/- 2.6 percent), and overall survival (71 +/- 2.6 percent) that were not significantly different from those observed after total mastectomy (54 +/- 2.4 percent, 62 +/- 2.3 percent, and 71 +/- 2.4 percent, respectively). There was no significant difference in the rates of distant-disease-free survival (P = 0.2) or survival (P = 0.3) among the women who underwent lumpectomy (with or without irradiation), despite the greater incidence of recurrence of tumor in the ipsilateral breast in those who received no radiation. We conclude that our observations through eight years are consistent with the findings at five years and that these new findings continue to support the use of lumpectomy in patients with Stage I or II breast cancer. We also conclude that irradiation reduces the probability of local recurrence of tumor in patients treated with lumpectomy.
1,544 citations
TL;DR: Tamoxifen significantly reduced the rate of treatment failure at local and distant sites, tumors in the opposite breast, and the incidence of tumor recurrence after lumpectomy and breast irradiation and was attained with a low incidence of clinically appreciable toxic effects.
Abstract: We conducted a randomized, double-blind, placebo-controlled trial of postoperative therapy with tamoxifen (10 mg twice a day) in 2644 patients with breast cancer, histologically negative axillary nodes, and estrogen-receptor-positive (greater than or equal to 10 fmol) tumors. No survival advantage was observed during four years of follow-up (92 percent for placebo vs. 93 percent for tamoxifen; P = 0.3). There was a significant prolongation of disease-free survival among women treated with tamoxifen, as compared with those receiving placebo (83 percent vs. 77 percent; P less than 0.00001). This advantage was observed in both the patients less than or equal to 49 years old (P = 0.0005) and those greater than or equal to 50 (P = 0.0008), particularly in the former, among whom the rate of treatment failure was reduced by 44 percent. Multivariate analysis indicated that all subgroups of patients benefited. Tamoxifen significantly reduced the rate of treatment failure at local and distant sites, tumors in the opposite breast, and the incidence of tumor recurrence after lumpectomy and breast irradiation. The benefit was attained with a low incidence of clinically appreciable toxic effects. The magnitude of the improvement obtained does not preclude the need for future trials in which patients given tamoxifen could serve as the control group in an evaluation of potentially better therapies. Tamoxifen treatment is justified in patients who meet the eligibility criteria of the present study and who refuse to participate in those trials. Since patients with tumors too small for conventional analysis of estrogen-receptor and progesterone-receptor concentrations were not eligible for this study, no information is available to indicate that such patients should receive tamoxifen.
1,421 citations
TL;DR: The results, although promising, do not obviate the need for additional trials to evaluate potentially better regimens of therapy, but they do suggest that sequential methotrexate-fluorouracil should be used in the control arm in such studies.
Abstract: We evaluated the postoperative use of sequential methotrexate and fluorouracil followed by leucovorin in 679 patients with primary breast cancer, histologically negative axillary nodes, and estrogen-receptor–negative (<10 fmol) tumors. No survival advantage was observed with this therapy as compared with no postoperative therapy during four years of follow-up (87 percent vs. 86 percent; P = 0.8). However, there was a significant prolongation of diseasefree survival among women who received this therapy as compared with those who did not (80 percent vs. 71 percent; P = 0.003). An advantage was observed in both the patients ≤ 49 years old and those ≥50. At four years, treatment failure was reduced by 24 percent in the younger group and by 50 percent in the older group. The rates of both local and regional and distant metastases were decreased. These benefits, achieved without the use of an alkylating agent, were associated with tolerable side effects. Multivariate analysis testing for potential int...
368 citations
Journal Article•
TL;DR: The findings presented refute the premise that removal of a primary tumor is a local phenomenon with no other biological consequences and indicate that, following primary tumor removal, metastatic behavior may be affected by an interplay of growth factor which can influence the outcome of a host to its tumor.
Abstract: The effect of removal of a primary tumor on the kinetics of cells in a metastasis was evaluated using six different tumors (C3H, MXTa, MXTb, MC54, CD8, and 3LL) which varied relative to their origin, histology, and the strain of mice in which they were carried. There was an increase in the labeling index (LI) of distant tumor focus ("metastasis") associated with the removal of each of the tumor types and unrelated to operative and anesthetic trauma. Information presented supports the presence of a serum growth factor as being responsible for the phenomenon. Serum obtained from mice following removal of a tumor, when transferred to a recipient with the same type of tumor as in the donor, resulted in an increase in the LI of the tumor. Multiple injections of serum failed to add to the increase but did prolong its presence, suggesting that there is a finite population of cells, most likely in the G1-G0 phase, which are capable of responding to the stimulating factor. The transfer of serum obtained following removal of a tumor type different from that in recipients resulted in findings which indicate that tumors producing a stimulating growth factor are those capable of responding to it. Serum obtained from animals with unremoved tumors or less than 18 h after removal failed to substantially augment the LI of tumors in recipients. It is postulated that the growth factor released by a tumor is in an inactive form which becomes activated over time. Observations indicate that medium conditioned by the growth of C3H tumor contains a growth-stimulating factor which is capable of increasing the LI of a C3H tumor in a recipient in a fashion similar to that obtained following tumor removal. That finding indicates the capability of the tumor to elaborate growth-stimulating material which may be similar to that found in serum. The findings presented refute the premise that removal of a primary tumor is a local phenomenon with no other biological consequences. They indicate that, following primary tumor removal, metastatic behavior may be affected by an interplay of growth factor(s) which can influence the outcome of a host to its tumor.
365 citations
Journal Article•
TL;DR: Evidence is provided indicating that serum obtained from mice treated with the antiestrogen tamoxifen and the luteinizing hormone-releasing hormone analogue Zoladex are equally effective in that regard and that serum received when transferred to a recipient bearing a tumor fails to stimulate DNA synthesis in the tumor of the recipient.
Abstract: This report indicates that not only does the preoperative administration of cyclophosphamide or radiation prevent the kinetic changes observed in a distant tumor focus following tumor removal but that the preoperative administration of the antiestrogen tamoxifen and the luteinizing hormone-releasing hormone analogue Zoladex are equally effective in that regard. It also provides evidence indicating that serum obtained from mice treated with those therapies when transferred to a recipient bearing a tumor of a similar type to that in the donor fails to stimulate DNA synthesis in the tumor of the recipient. In contrast, an increase in labeling index occurs following transfer of serum obtained following tumor removal from untreated mice. Moreover, when tumor-bearing mice were treated by each of the four modalities prior to receiving serum obtained from untreated donors following removal of a tumor, no kinetic changes were observed in the tumor of the serum recipient.
149 citations
TL;DR: It is concluded that numbers of eosinophils and mast cells may play a role in the natural history of rectal cancer but only the latter represents a prognostic parameter independent of Dukes' stage or nodal status.
116 citations
111 citations
TL;DR: It is suggested that the use of confusing subscripts is unnecessary and the Dukes' staging method is the simplest and most consistent algorithm related to prognosis.
Abstract: The relative prognostic value of the Dukes, Astler, and Coller and TNM staging systems was evaluated for 745 pathologically evaluable patients with rectal cancer enrolled in protocol R-01 of the National Surgical Adjuvant Breast and Bowel Projects. All three methods were found to be highly interrelated. However, the magnitude and consistency of prognostic discrimination among stages was best exhibited by the Dukes' and TNM systems. Survival was comparable among patients with Astler and Coller A and B1 and TNM T1N0M0 and T2N0M0 lesions. Since neither method improved on the predictability noted in Dukes' A cases it is suggested that the use of confusing subscripts is unnecessary. On the other hand, striking prognostic discrimination was observed when Dukes' C cases were subdivided according to depth of tumor penetration as proposed by Astler and Coller and designated as C1 and C2. Multivariate analyses revealed this feature to be independent of number of nodal metastases (1-4 versus 5+ positive), their site (near or far from the growth), or degree of tumor differentiation. The site of nodal metastases appeared to be related to numbers of nodal metastases rather than site per se. Considerations of the findings indicate that the Dukes' staging method is the simplest and most consistent algorithm related to prognosis. The only modification that would enhance its value in this regard would be the subdivision of C cases according to the criteria of Astler and Coller rather than that proposed by Dukes himself.
77 citations
TL;DR: The disease-free survival of all cohorts of node-negative patients with estrogen-receptor-negative or estrogen- receptor-positive tumors was poor enough to justify systemic treatment, and the benefits of the therapies used are insufficient to eliminate the need for assessing putatively better regimens.
Abstract: OBJECTIVE To determine whether in the previous National Surgical Adjuvant Breast and Bowel Project (NSABP) studies of node-negative breast cancer there were either cohorts of patients with a prognosis favorable enough to preclude using systemic therapy or subsets of patients who failed to benefit from the treatments. DESIGN Randomized clinical trials with stratification after surgery. SETTING NSABP trials at institutions in the United States and Canada. PATIENTS Data were collected on 731 eligible patients (Protocol B-13) with estrogen-receptor-negative tumors who randomly received either no therapy after surgery or sequential methotrexate and fluorouracil (M----F) followed by leucovorin. Data were also collected on 2834 patients (Protocol B-14) with estrogen-receptor-positive tumors who randomly received either placebo or tamoxifen treatment. The percentage of patients surviving disease-free was determined through 4 years of follow-up using life-table estimates. INTERVENTIONS Protocol B-13 patients received 12 courses of M----F given intravenously on days 1 and 8 every 4 weeks. Leucovorin therapy was begun 24 hours after M----F administration. Protocol B-14 patients received 5-year treatment with either tamoxifen (10 mg twice daily by mouth) or placebo. RESULTS When the outcome of untreated patients in either trial was related to the stratification variables, women were found to have a disease-free survival of less than 80% through 4 years of follow-up. This percentage is apt to decrease because the probability of treatment failure increases with time. In both trials, all subsets of women benefited from M----F or tamoxifen therapy. CONCLUSIONS The disease-free survival of all cohorts of node-negative patients with estrogen-receptor-negative or estrogen-receptor-positive tumors was poor enough to justify systemic treatment. The benefits of the therapies used are insufficient to eliminate the need for assessing putatively better regimens.
38 citations
35 citations
TL;DR: The findings indicate that the Jass system is a valid prognostic method for patients with rectal carcinoma and warrant its continued use for prognosis and therapeutic decisions for patientswith rectal cancer.
Abstract: A comparison of the prognostic values of the Dukes and Jass systems were performed with 722 patients with rectal cancer enrolled in the National Surgical Adjuvant Breast and Bowel Projects, protocol R-01. The Jass system revealed four prognostic groups when all patients or only Dukes' B and C cases were examined; however, the magnitude of differences between groups I and II and III and IV were small. Dukes' classification, as defined in this study, revealed five prognostic groups. A statistically strong association between the Jass and Dukes systems was observed. Although histologic grade permitted further prognostic discrimination of all Dukes stages except A, only the Jass system allowed for the subdivision of C cases with up to four nodes positive for metastases. Those in that group had survival rates comparable to B cases (no nodal involvement) when scores of I and II were found. The distributions of the patients in the extremes of the Jass and Dukes systems (C2 as defined) were almost similar. The findings indicate that the Jass system is a valid prognostic method for patients with rectal carcinoma. In this material, however, it basically allowed for only two major prognostic groups whereas five were noted by the Dukes method. These results, as well as the more objective nature of Dukes' classification, warrant its continued use for prognosis and therapeutic decisions for patients with rectal cancer.
TL;DR: It is concluded that an additional year of tamoxifen therapy, following the completion of chemotherapy prolongs both disease-free survival and actual survival in node-positive, 'tamoxifens-responsive' patients.
Abstract: The aim of the present investigation was to determine whether the administration of a third year of tamoxifen, following 2 years of L-phenylalanine mustard, 5-fluorouracil and tamoxifen, would benefit