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Biomedical subjects

B Fisher

Publications and source records attributed to B Fisher.

At least 289 records · Page 16Linked to original sources
PubMed1983

Types of tumor lymphoid response and sinus histiocytosis. Relationship to five-year, disease-free survival in patients with breast cancer.

Diffuse (D), perivascular (PV), and a combination form (DPV) of lymphoid infiltrates were found in 95% of invasive breast cancers. The DPV and D patterns were associated with tumor necrosis, and the D pattern with cancers of nuclear grade 3 (most anaplastic) and histologic grade 3 (most malignant). An absent cell reaction was significantly related to absent nodal metastases. Life-table analyses disclosed a higher incidence of patients' being disease free for five years when no cell reaction was encountered. There was no significant association between the presence or absence of any particular type of sinus histiocytosis (SH) of regional lymph nodes and five-year, disease-free survival. It is uncertain whether lymphoid reactions and SH represent immunologic host responses, but if they do, they appear to be biologically ineffectual and, in the former instance, perhaps even detrimental.

Breast Neoplasms↗
PubMed1983

Influence of the interval between primary tumor removal and chemotherapy on kinetics and growth of metastases.

In many animal models, primary tumor removal produces increased proliferation of cells in metastatic foci. The present investigations using a murine mammary tumor were carried out to determine how a variation in the time interval between primary tumor removal and administration of a single dose of cyclophosphamide (CY) affected labeling indices of residual tumor cells, their growth, and animal survival. The CY (240 mg/kg) had a more favorable effect when given on the day of tumor removal than 3 days after, a time when the labeling index (LI) of metastases was at a peak. It was least effective if given at 7 days following primary tumor excision, when the LI had returned to the preoperative level. The greatest effect occurred when the CY was given prior to operation. It completely prevented the increase in LI resulting from tumor removal, more effectively suppressed the growth of residual tumor, and prolonged survival to a greater extent than was noted under any other circumstance. The interval between tumor removal and administration of a relatively small amount of CY (60 mg/kg) was critical. When given on the day of tumor removal, an increase in LI of the residual focus occurred which was greater than that occurring as a result of tumor removal. When given 3 days after tumor removal, the smaller dose was almost as effective in suppressing LI as was the larger. From a kinetic standpoint, there was no advantage in reducing the tumor burden prior to the use of chemotherapy. The tumor response in this model suggests that, for the most effective control of metastases, the largest tolerable dose of chemotherapy would best be used at the time of or before primary tumor removal. The results provide a biological rationale for the use of perioperative adjuvant chemotherapy.

Adenocarcinoma↗
PubMed1982

Impact of randomized clinical trials on therapy of primary breast cancer: the NSABP overview.

The history of treatment for early breast cancer, particularly as it relates to the most recent calendar decade, exemplifies the contribution that can be made to resolving therapeutic controversies by well-designed prospective randomized clinical trials (RCTs). In this article we provide an overview of the breast cancer clinical trials that have been conducted by the National Surgical Adjuvant Project for Breast and Bowel Cancers (NSABP) since 1971. These trials have had a strong impact in changing the clinical management of breast cancer over the past decade. Emphasis will be given to those aspects of the studies that demonstrate the advantages and/or necessity for RCTs to evaluate alternative therapeutic approaches to the management of breast cancer.

Antineoplastic Agents↗
PubMed1981

Findings from NSABP Protocol No. B-04: comparison of radical mastectomy with alternative treatments. II. The clinical and biologic significance of medial-central breast cancers.

Findings from 1665 women with primary breast cancer, treated at 34 NSABP institutions in Canada and the United States, have failed to demonstrate that patients with medial-central tumors had a greater probability of developing distant metastases or dying than did those with lateral tumors despite the greater incidence of internal mammary (IM) node involvement when tumors are medial-central in location. A comparison of patients with similar clinical nodal status and tumor location who were treated either by radical mastectomy (RM) or by total mastectomy plus radiation therapy (TM + RT) failed to indicate that radiation of IM nodes reduced the probability of distant treatment failure (TF) or mortality. When findings from patients having equivalent clinical nodal status and tumor location treated by TM alone or TM + RT were compared, it was found that the addition of RT failed to alter the probability of the occurrence of a distant TF or of death. This was despite the fact that in the nonradiated group two putative sources of further tumor spread, i.e., positive axillary and IM nodes, were left unremoved and untreated. The findings provide further insight into the biologic significance of the positive lymph node and confirm our prior contention that positive regional lymph nodes are indicators of a host-tumor relationship which permits the development of metastases and that they are not important investigators of distant disease.

Axilla↗
PubMed1981

Disease-free survival at intervals during and following completion of adjuvant chemotherapy: the NSABP experience from three breast cancer protocols.

Findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) trials evaluating three different regimens of adjuvant chemotherapy (L-PAM, L-PAM + 5-FU, L-PAM + 5-FU + MTX) in patients with primary breast cancer and positive axillary nodes indicate that each regimen has significantly contributed toward achieving the initial goal of such therapy, namely to diminish or prevent treatment failure in all or major subsets of patients during the first two years following operation when women are at greatest risk for a recurrence. Because of this hazard, chemotherapy was administered in all protocols for two years. Findings were examined at the end of the first year of therapy and at the termination of the second year for those who entered that year of therapy disease-free in order to determine whether the second year of treatment contributed a benefit beyond that achieved from the first year of therapy. A reduction in the incidence of treatment failure was evident in every subgroup of patients at completion of the first year of therapy. There was evidence of added improvement during the second year of treatment in patients aged 49 years or younger but not in those aged 50 years or older. Despite the finding, it is not possible from these studies to be absolutely certain that a second year of therapy is or is not advantageous. Findings obtained to date from the three studies indicate that patients completing two years of chemotherapy who are disease-free display a subsequent treatment failure rate that is no greater than that observed in untreated patients who survived two years without recurrence. Consequently, any advantage in disease-free survival observed at completion of therapy has been subsequently sustained for several years, suggesting this represents a real decrease rather than a postponement of treatment failure.

Age Factors↗
PubMed1981

Treatment of primary breast cancer with chemotherapy and tamoxifen.

We studied the possibility that the addition of tamoxifen to L-phenylalanine mustard combined with 5-fluorouracil enhances the benefit from the latter two drugs that has been observed in women with primary breast cancer and positive axillary nodes. Recurrence of disease was reduced at two years in patients given the three-drug regimen whose tumor estrogen-receptor levels were greater than or equal to 10 fmol. Among patients greater than or equal to 50 years old treatment failure was significantly reduced (P less than 0.001): by 51 per cent in those with one to three positive nodes and by 64 per cent in those with four or more. Higher receptor levels were associated with a greater probability of disease-free survival. Patients less than or equal to 49 years old were less responsive: those with one to three positive nodes received no benefit from tamoxifen at any receptor level, whereas those with four or more appeared to have reduced treatment failure associated with higher receptor levels. This adjuvant chemotherapy is not indicated in patients less than or equal to 49 years old whose tumor receptor levels are below 10 fmol; there is a suggestion of benefit in patients greater than or equal to 50 years old whose levels are low.

Age Factors↗
PubMed1981

Surgery in the primary treatment of breast cancer.

Information available from NSABP protocols has contributed to an altered biological perception of breast cancer. The results of these studies lend support to a hypothesis which postulates that alterations in the loco-regional treatment of primary breast cancer will not change the natural history of the disease relative to distant metastasis and survivorship. Data from NSABP Protocol B-04 indicate that radical mastectomy provides no advantage over total mastectomy in clinically node-negative patients. Since 39% of this population had histologically positive nodes it may be concluded that leaving histologically positive nodes untreated results in no disadvantage. NSABP Protocol B-04 made available the scientific rationale for the study of breast-preserving operations in which the clinical significance of multicentricity will be determined. Although there is a sound scientific basis for the consideration of segmental mastectomy, there are no data available to justify the utilization of the procedure outside the context of a clinical trial. With the increased popularity and implementation of breast-preserving operations without the necessary supporting data, a potentially dangerous situation has been created which threatens to undermine the clinical trial process.

Axilla↗
PubMed1981

A commentary on the role of the surgeon in primary breast cancer.

The function of the surgeon remains the same relative to the management of primary breast cancer. What has changed is our perception of the biology of the disease and our understanding of data evaluation and analysis. This presentation provides an overview of some of the more important findings which have altered our understanding of breast cancer and which have led to a reassessment of the basis for cancer surgery. It also emphasizes why controlled clinical trials are necessary for obtaining credible data. To most succinctly summarize the author's position regarding a number of critical controversies related to primary breast cancer surgery, answers are presented to ten of the questions most frequently posed by surgeons regarding surgical therapy.

Axilla↗
PubMed1981

Correlation of primary breast cancer histopathology and estrogen receptor content.

We studied the association of estrogen receptor (ER) with several histologic variables that correlate with breast tumor differentiation and with patient prognosis. Contingency table analysis revealed highly statistically significant correlations between ER content and histologic and nuclear grades, tumor necrosis, and the degree of elastosis and lymphoid cell infiltration. ER positive tumors were more likely than ER negative tumors to demonstrate histological evidence of tumor differentiation. All tumors with histologic grade 1 or nuclear grade 1 (best differentiated) were ER positive or borderline positive. Eighty-nine percent of ER negative tumors were histologic grade 3 and 78.4% were nuclear grade 3 (poor differentiation). ER positive tumors were also correlated with absent tumor necrosis, higher elastic content, and absent lymphoid cell infiltration, all features of good differentiation. Medullary carcinomas were frequently (73%) ER negative, but no relationship between ER and other morphologic types of breast cancer or 9 other morphologic variables was found. ER appears to be a biochemical marker for the degree of differentiation of human breast cancer providing a rationale for the observed differences in biological behavior between receptor positive and negative tumors.

Axilla↗
PubMed1980

The contribution of recent NSABP clinical trials of primary breast cancer therapy to an understanding of tumor biology--an overview of findings.

Disagreement about local-regional management of primary breast cancer is related to differences in perception of the biology of the disease. Other factors are secondary and obscure the reality that all treatment must be related to biological considerations; otherwise, the basis for therapy is relegated to speculation and to personal experience. As a result of extensive laboratory and clinical studies during the past two decades, there has arisen an altered concept of cancer biology. The National Surgical Adjuvant Project for Breast and Bowel Cancers (NSABP) has made a major contribution to the change through findings from a series of prospective randomized clinical trials. That group of American and Canadian investigators has implemented a series of trials aimed at answering biological as well as clinical questions. Those studies have not only been concerned with defining proper local-regional treatment but have also pointed out the need for, and value of, systemic therapy when used in conjunction with operation. This report will provide an overview of past and present NSABP contributions and will consider those findings in relation to observations from other clinical trials of pertinence. It will emphasize that controversies concerning breast cancer management are related to biological issues that cannot be resolved by "populism" or appeals to emotion.

Adult↗