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Biomedical subjects

B Fisher

Publications and source records attributed to B Fisher.

At least 217 records · Page 12Linked to original sources
PubMed1987

Prolonging tamoxifen therapy for primary breast cancer. Findings from the National Surgical Adjuvant Breast and Bowel Project clinical trial.

OBJECTIVE: To determine whether prolonging the duration of tamoxifen administration beyond the cessation of a combined chemotherapy regimen benefits patients with primary breast cancer with positive findings in axillary nodes who benefit initially from the combined regimen. DESIGN: Nonrandomized, nonconcurrent cohort study. SETTING: National Surgical Adjuvant Breast and Bowel Project, conducted in 68 institutions in North America. PATIENTS: Women were included if they had breast cancer with positive nodes and were aged 49 years or less with both estrogen and progesterone receptor levels of 10 fmol or more, aged 50 to 59 years with progesterone receptor levels of 10 fmol or more, or aged 60 to 69 years. Two cohorts were compared: patients who were randomly assigned to the tamoxifen arm of the adjuvant chemotherapy trial (randomized patients) and women who were added to this arm after randomization had ceased (registered patients). Three hundred seventy-seven women in each group who were disease free at the end of the initial 2-year treatment period were followed for an additional 3 years. INTERVENTIONS: All received melphalan, fluorouracil, and tamoxifen (10 mg twice daily by mouth) for 2 years. Registered patients (but not randomized patients) were offered tamoxifen for a third year after the initial 2-year treatment period, and 273 (72%) agreed. MEASUREMENTS AND MAIN RESULTS: Women receiving a third year of tamoxifen had a better disease-free survival rate (odds ratio, 1.54; 95% confidence interval, 1.14 to 2.07; p = 0.004) and survival rate (odds ratio, 1.56; 95% Cl, 1.02 to 2.37; p = 0.04) through their fifth postoperative year. Women aged 50 years or more benefited, but those aged 49 years or less did not. CONCLUSIONS: The benefit of tamoxifen given to tamoxifen-responsive patients in conjunction with melphalan and fluorouracil appears to be enhanced when the tamoxifen treatment is continued beyond cessation of treatment with these agents.

Actuarial Analysis↗
PubMed1987

Overview of randomized trials of postoperative adjuvant radiotherapy in breast cancer.

An overview of the mortality results of the mature trials in which radiotherapy was a randomized option after simple or radical mastectomy is presented. The principal aim of the overview was to study long-term survival, and recent trials, often including chemotherapy options, have not been included. A total of 7941 patients were entered into these trials and 4148 deaths occurred. No differences were found in survival in the first 10 years of follow-up, in trials employing either radical mastectomy or simple mastectomy. Follow-up information after 10 years came mostly from trials employing radical mastectomy with or without irradiation, and in these trials a significant excess of deaths was observed among patients given radiotherapy (P less than 0.001, all trials; P = 0.002, radical mastectomy trials only). Further data collection will be necessary to determine which causes of death are elevated.

Breast Neoplasms↗
PubMed1987

Overview of randomized trials comparing radical mastectomy without radiotherapy against simple mastectomy with radiotherapy in breast cancer.

An overview of mortality in the mature randomized trials comparing radical mastectomy without radiotherapy against simple mastectomy with radiotherapy has been conducted. These trials mark a transitional period between radical mastectomy and simple mastectomy as the generally preferred surgical treatment and as such are not strictly trials assessing the value of postoperative adjuvant radiotherapy. All known mature trials have been included and these four trials have entered a total of 3236 patients, in whom 1678 deaths have been recorded. Overall, no significant difference in survival was seen, but there was a nonsignificant trend for patients given radiotherapy to do worse after 15 years of follow-up.

Breast Neoplasms↗
PubMed1987

The technique of segmental mastectomy (lumpectomy) and axillary dissection: A syllabus from the National Surgical Adjuvant Breast Project workshops.

Surveys conducted by the American College of Surgeons indicate an increasing trend toward the treatment of primary breast cancer by segmental mastectomy and radiotherapy. This operation has never been formally taught in training programs, and scant standard descriptive material exists. The National Surgical Adjuvant Breast Project conducted a series of workshops to develop guidelines for the performance of the operation. The essential points are (1) pathologic control of margins to ensure complete surgical excision, (2) surgical principles of complete tumor excision, (3) attention to optimum cosmetic results, and (4) axillary dissection for accurate staging and regional control of the disease. This article summarizes the recommendations made at those workshops.

Axilla↗
PubMed1987

Incidence and characteristics of McCollough aftereffects following video display terminal use.

After using video display terminals (VDT), some persons notice that achromatic patterns appear faintly colored hours after terminal use. We investigated the incidence of this effect, the McCollough effect (ME), among 125 VDT users. Subjects completed a questionnaire regarding work habits and certain life-style aspects. They were shown photographs of varying spatial frequencies to identify the adapting stimulus responsible for the ME. The incidence of ME after routine use of VDTs was 19.1%. The adapting stimulus was the repeating character lines of the VDT. No aspect of life-style investigated appeared to predispose an individual to develop the ME. Those subjects who developed the ME did not differ from those who did not in age, sleep, caffeine consumption, use of medication, refractive errors, or computer usage, nor did they have a higher incidence of ocular defects or eye strain.

Computer Systems↗
PubMed1986

Pathologic findings from the National Surgical Adjuvant Breast Project (protocol 6). II. Relation of local breast recurrence to multicentricity.

One hundred ten local breast recurrences were observed in 1108 pathologically evaluable patients enrolled in NSABP protocol 6 who were treated by lumpectomy and followed for 5 to 95 months (average, 39 months). Eighty-six percent and 95% of all local breast recurrences were noted within 4 and 5 years, respectively, following lumpectomy. Life table analysis revealed their incidence to be 24% for those not and 6% for those receiving lumpectomy and breast irradiation. One hundred four (95%) of the breast recurrences involved the mammary parenchyma and the remaining 6 (5%) involved the skin and/or nipple only. Eleven (10%) of the former were noninvasive. The most common (86%) presentation of breast recurrence appeared to be a localized mass within or close to the quadrant of the index cancer. In 14% the recurrence not only involved the same quadrant, but was more diffuse within the breast extending to remote areas as well. This type was characterized pathologically by marked intralymphatic extension as well as involvement of the overlying skin and/or nipple after the fashion of so-called inflammatory or occult inflammatory breast cancer. The recurrences noted in the skin and/or nipple only were also pathologically characterized by intralymphatic involvement at these sites in the majority of instances. These two forms of breast recurrences appear to reflect the localized growth of highly aggressive invasive breast cancers. The concordance of histologic types and grades of the index and recurrent cancers implies that such events represent growth of overlooked tumor, a deficiency attendant with lumpectomy due to the extreme multifocal nature (not multicentricity) of some breast cancers and/or inadequacies in evaluating the lines of resection of lumpectomy specimens. Sources of error in regard to this latter are identified and guidelines for the examination of such specimens, as well as the assessment of margins, are presented. The observation that local breast recurrences noted following lumpectomy occurred within or close to the same quadrant as the index cancer, despite the presence of multicentric noninvasive cancers in 10% of the patients treated by total mastectomy, minimizes the biological and clinical significance of multicentric foci of cancer present in some breast cancers. Cancer measuring greater than or equal to 2.0 cm, having high histologic and nuclear grades, or intralymphatic extension, were found to have a statistically significant association with local breast recurrence in all patients following lumpectomy. A converse relationship was noted with tubular and scar cancers of types 1 and 4.(ABSTRACT TRUNCATED AT 400 WORDS)

Actuarial Analysis↗
PubMed1986

Giving patients their own records in general practice: experience of patients and staff.

Patients have reacted positively to seeing their medical records in a general practice which has a predominantly working class population in south east London. Most patients were familiar with the information in their records. Older people tended to avoid reading their notes. There have been few inaccuracies and unpleasant reactions reported, and few problems have arisen.

Aged↗
PubMed1986

Pathologic findings from the National Surgical Adjuvant Breast Project (protocol 6). I. Intraductal carcinoma (DCIS).

Seventy-eight examples of intraductal carcinoma (DCIS) were identified after pathologic review of 2072 specimens obtained from National Surgical Adjuvant Breast Project protocol 6. This randomized clinical trial compares the therapeutic merit of total mastectomy (TM) with lumpectomy (L), with (LX) and without (LO) postoperative irradiation. All patients were subjected to axillary lymph node dissection. Seven (14%) of the 51 patients with DCIS treated by L exhibited breast recurrence within or close to the site of the initial lesion 4 to 53 months (average, 16 months) after L. Only 2 (7%) of these events occurred in the 29 women treated by LX, as opposed to 23% in the LO group. No pathologic features were noticed that might have been considered predictive of local breast recurrence. The three DCIS recurrences and the four invasive forms noted are considered to represent overlooked or incompletely excised foci of cancer because of the multifocality (not multicentricity) of some breast cancers. The possibility that DCIS may represent a marker of risk for the development of cancer rather than a precursor lesion per se is suggested. Despite apparent difficulties in the pathologic diagnosis of DCIS as well as uncertainty concerning its natural history, no evidence was found to indicate that it represents a more ominous disease than invasive cancer. Indeed, treatment failure occurred in only one patient treated by LX and a similar number subjected to TM (4% versus 2%). Although these observations are short term (average follow-up, 39 months), estimates of the probability of local recurrence or survival suggest that they will not be significantly altered after longer periods of surveillance. Thus, there are no compelling reasons why DCIS may not be treated in a cosmetically acceptable manner by LX. A randomized clinical trial addressing this issue is now in progress.

Basement Membrane↗
PubMed1986

Tumor nuclear grade, estrogen receptor, and progesterone receptor: their value alone or in combination as indicators of outcome following adjuvant therapy for breast cancer.

Previous reports by us have shown that the outcome of breast cancer patients who have received systemic adjuvant therapy is influenced by tumor estrogen or progesterone receptor (ER or PR) content or by nuclear grade. This publication provides information regarding the relative merit of those three markers. Findings from patients receiving L-PAM plus 5-FU (PF) or PF plus tamoxifen (PFT) indicate that the disease-free survival and survival within each regimen was almost identical when related to either ER, PR, or nuclear grade. Those having tumors with either of the receptors greater than or equal to 10 fmol or a good nuclear grade had a better outcome through five postoperative years than did those with ER or PR 0-9 fmol or poor nuclear grade. The magnitude of the difference was similar for each of the three discriminants. Since they were found to be of equal predictive value, one marker might well serve as a substitute for another. Cox regression analyses, however, clearly indicate that ER, PR, and nuclear grade have an independent influence on outcome and that a more accurate assessment of outcome is obtained when more than one marker is employed. Thus, information should be obtained on as many markers as possible. This conclusion is supported by observations presented which indicate that nuclear grade in combination with either or both of the receptors is a better predictor than either marker alone and that, as indicated by life table probability values and relative odds ratios, an increasing number of favorable tumor prognostic indicators results in a better patient outcome particularly in PFT-treated patients. A possible explanation is considered for why the separation of receptor/nuclear grade categories is more orderly and pronounced in PF-treated patients receiving tamoxifen than in those given PF alone.

Aged↗
PubMed1986

A comparison of stapled and handsewn anastomoses in patients undergoing resection for Dukes' B and C colorectal cancer. An analysis of disease-free survival and survival from the NSABP prospective clinical trials.

This study was to assess the effect of stapled colorectal anastomoses on local recurrence, disease-free survival, and survival following curative resection for Dukes' B and C adenocarcinoma. Data were derived from two randomized prospective trials of the National Surgical Adjuvant Breast and Bowel Project designed to evaluate the efficacy of adjuvant therapy in colorectal cancer. Of 1111 patients with colonic anastomoses, 255 were stapled mechanically. There were no significant differences in disease-free survival, survival, or local tumor recurrence among patients subjected to stapled or handsewn anastomoses. Of the 181 patients undergoing anterior resection for rectal cancer, 82 anastomoses were fashioned with staples. No significant disadvantage in disease-free survival, survival, or local recurrence could be attributed to use of the mechanical stapling devices. Twelve percent of patients undergoing stapled rectal anastomoses developed a local recurrence as a first sign of treatment failure compared with 19 percent for the handsewn group. No significant differences in the length of distal margins were detectable. The average time on study was 41 months. The use of stapled anastomoses for carcinoma of the colon or rectum is not associated with an adverse effect on long-term outcome.

Adenocarcinoma↗
PubMed1986

Influence of irradiation of a primary tumor on the labeling index and estrogen receptor index in a distant tumor focus.

The present investigation reaffirms our observation that removal of a C3H mouse mammary adenocarcinoma results in a perturbation of tumor cells in a metastatic focus. An increase occurs in the proportion of cells undergoing DNA synthesis (labeling index, LI), and a decrease occurs in the proportion demonstrating estrogen receptor (ER index; ERI). The changes are transient but of sufficient duration and magnitude to produce an increase in the size of a distant tumor. This study was conducted to determine whether cytoreduction of a primary tumor by irradiation would produce a similar change in metastatic tumor cells and whether preoperative radiation would obtund the effect of primary tumor removal. The administration of a maximum tolerated dose of radiation (50 Gy) to a primary tumor produced a significant (p less than 0.001) increase in LI and decrease in ERI of a lesser magnitude than that observed following surgical removal of the primary tumor, but still sufficient to enhance the growth of a metastatic focus. Whereas, there was almost a 50% increase in LI in a metastasis 1 and 3 days following removal of a primary tumor the increase was only 13% three days after radiation. There was a 20% decrease in ERI 3 days following radiation and a 37% decrease at that time following tumor removal. Preoperative irradiation of a primary tumor 1, 3, or 5 days prior to tumor removal, obtunds the increase in LI and decrease in ERI following operation. Radiation the day before surgery was most effective because the changes in a distant focus occurring as a result of the radiation and of the surgery were prevented. The clinical relevance of these observations deserves further consideration.

Animals↗
PubMed1986

The prognostic value of the modifications of the Dukes' C class of colorectal cancer. An analysis of the NSABP clinical trials.

This study was carried out in an effort to resolve the dilemma created by three proposed modifications of the Dukes' C class of colorectal cancer. Each modification is based on a separate prognostic discriminant characterized by: the level of histologically positive nodes, the depth of tumor penetration, and the number of histologically positive nodes. Data were derived from 844 patients with Dukes' C lesions randomized into two prospective clinical trials of the NSABP; the mean time on study was 41 months. Analysis of the three modifications as independent variables without regard for possible confounding effects disclosed that each had a highly significant predictive capacity. When each discriminant was examined, this time adjusting for the contribution of the other two discriminants, the effect attributable to the level of positive nodes was markedly attenuated. Thus, the level of positive nodes provided little information over and above that of depth of tumor penetration and the number of positive nodes. Of the two latter discriminants, although both were significant predictors of survival, the number of positive nodes appeared to be the strongest factor. Using both depth of penetration and the number of positive nodes, a unique Dukes' C subset of patients could be identified with a prognosis at least as good as Dukes' B lesions; this group was characterized by partial tumor penetration and the presence of 1-4 positive nodes. It is concluded that both depth of penetration and the number of positive nodes represent appropriate modifications of the initial Dukes scheme, and one discriminant should not be used to the exclusion of the other. The data raise serious doubts relative to the propriety of newly proposed TNM classification schemes that fail to utilize the number of positive nodes as a predictive discriminant.

Carcinoma↗
PubMed1986

An analysis of survival and treatment failure following abdominoperineal and sphincter-saving resection in Dukes' B and C rectal carcinoma. A report of the NSABP clinical trials. National Surgical Adjuvant Breast and Bowel Project.

Abdominoperineal resections for rectal carcinoma are being performed with decreasing frequency in favor of sphincter-saving resections. It remains, however, to be unequivocally demonstrated that sphincter preservation has not resulted in compromised local disease control, disease-free survival, and survival. Accordingly, it is the specific aim of this endeavor to compare local recurrence, disease-free survival, and survival in patients with Dukes' B and C rectal cancer undergoing curative abdominoperineal resection or sphincter-saving resection. For the purpose of this study, 232 patients undergoing abdominoperineal resection and 181 subjected to sphincter-saving resections were available for analysis from an NSABP randomized prospective clinical trial designed to ascertain the efficacy of adjuvant therapy in rectal carcinoma (protocol R-01). The mean time on study was 48 months. Analyses were carried out comparing the two operations according to Dukes' class, the number of positive nodes, and tumor size. The only significant differences in disease-free survival and survival were observed for the cohort characterized by greater than 4 positive nodes and were in favor of patients treated with sphincter-saving resections. A patient undergoing sphincter-saving resection was 0.62 times as likely to sustain a treatment failure as a similar patient undergoing abdominoperineal resection (p = 0.07) and 0.49 times as likely to die (p = 0.02). The inability to demonstrate an attenuated disease-free survival and survival for patients treated with sphincter-saving resection was in spite of an increased incidence of local recurrence (anastomotic and pelvic) observed for the latter operation when compared to abdominoperineal resection (13% vs. 5%). A similar analysis evaluating the length of margins of resection in patients undergoing sphincter-preserving operations indicated that treatment failure and survival were not significantly different in patients whose distal resection margins were less than 2 cm, 2-2.9 cm, or greater than or equal to 3 cm. If any trend was observed, it appeared that patients with smaller resection margins had a slightly prolonged survival (p = 0.10). This observation was present in spite of the fact that local recurrence as a first site of treatment failure was greater in the group with less than 2 cm that it was in the greater than or equal to 3 cm category, 22% versus 12%. This increased local recurrence rate in the population with smaller margins was not translated into an in crease in overall treatment failure and had absolutely no influence on survival. It is suggested that local recurrence serves as a marker of distant disease.(ABSTRACT TRUNCATED AT 400 WORDS)

Anal Canal↗
PubMed1986

Adjuvant chemotherapy with and without tamoxifen in the treatment of primary breast cancer: 5-year results from the National Surgical Adjuvant Breast and Bowel Project Trial.

In this National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trial, 1,891 women with primary operable breast cancer and positive axillary nodes were randomized between Jan, 1977 and May 1980 to receive L-phenylalanine mustard (L-PAM) and 5-fluorouracil (5-FU) either with or without tamoxifen (TAM)-PFT. This report presents life table probabilities, cumulative odds ratios, and P values for disease-free survival (DFS) and survival at yearly intervals through 5 years of observation (mean time on study, 72 months). When patients were examined overall without regard for any discriminant associated with outcome, ie, age, number of positive nodes, or tumor receptor status, there was a significant prolongation of DFS (P = .002), but not survival through the fifth postoperative year. The benefit was almost entirely restricted to those greater than or equal to 50 years with greater than or equal to 4 positive nodes. In that group there was a 66% greater chance of remaining disease free if PFT was received (P less than .001), and there was also a significant survival benefit (P = .02). The advantage from PFT was found to be associated with tumor estrogen receptor (ER) and progesterone receptor (PR) as well as patient age and nodal status. Overall there was a significant improvement in DFS from PFT in those having tumors with an ER or PR level greater than or equal to 10 femtomole (fmol) (P = .01 and .009, respectively). No significant benefit in DFS or survival has been observed in patients less than or equal to 49 years old related either to nodes or tumor receptor status. Survival continues to be adversely affected by TAM in those patients (less than or equal to 49 years old), particularly when their tumors have a PR of 0 to 9 fmol (P = .007). In patients greater than or equal to 50 years old with four or more positive nodes, a significant DFS benefit persisted through the fifth year of observation in those having tumor ER or PR levels greater than 10 fmol (P less than .001 and .002). The advantage was observed in patients 50 to 59 years old as well as those 60 to 70. Women in the older decade demonstrated some advantage from PFT when their tumor ER or PR was 0 to 9 fmol. The most likely explanation for this finding is analytical error in receptor analyses.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1986

Ten-year results from the National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trial evaluating the use of L-phenylalanine mustard (L-PAM) in the management of primary breast cancer.

Between 1972 and 1974, patients were entered into a National Surgical Adjuvant Breast and Bowel Project (NSABP) trial to evaluate L-phenylalanine mustard (L-PAM) as an adjuvant to mastectomy in patients with primary breast cancer and pathologically positive axillary nodes. Overall, findings through 10 years of observation indicate an 8% difference in disease-free survival (DFS) (P = .06) and a 5% difference in survival (P = .4). Women less than or equal to 49 years of age who received L-PAM demonstrate a significant (P = .03) prolongation of DFS and a significant (P = .05) survival benefit compared with those who received a placebo. There is a 37% reduction in their mortality and a cumulative odds of survival of 1.67. In that age group, both those with one to three and greater than or equal to 4 positive nodes benefited, but the advantage was greater when there were fewer positive nodes. There was a significant (P = .009) reduction in mortality (64%) and a cumulative odds of survival of 3.25 in patients less than or equal to 49 years old with one to three positive nodes. No advantage from L-PAM was observed in patients greater than or equal to 50 years old. When L-PAM response is related to nuclear grade, a marker of tumor differentiation, there is a highly significant improvement in DFS (less than .001), distant DFS (.001), and survival (.004) through 10 years of observation for all patients with tumors classified as nuclear grade poor (poorly differentiated), regardless of age and nodal status. Mortality was reduced by 32% and the cumulative odds of survival was 2.10 at 10 years. Of singular importance is the observation of a benefit in those greater than or equal to 50 years of age as well as in those less than or equal to 49 years of age with poorly differentiated tumors. There is a significant (P = .003) survival benefit for those in the older age group with a 37% reduction in mortality, and a cumulative odds of survival of 2.75. Patients in both age groups with well-differentiated tumors demonstrated no benefit from L-PAM. Those who are older seem to do less well following chemotherapy. We conclude that tumor differentiation is a better discriminant of response to chemotherapy than is age, and that both younger and older women are responsive to adjuvant chemotherapy when they have poorly differentiated tumors.

Actuarial Analysis↗