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Biomedical subjects

B Fisher

Publications and source records attributed to B Fisher.

At least 235 records · Page 13Linked to original sources
PubMed1986

Systemic adjuvant therapy in treatment of primary operable breast cancer: National Surgical Adjuvant Breast and Bowel Project experience.

This report provides an overview of information presented by us at a recent National Institutes of Health Consensus Development Conference on Adjuvant Chemotherapy. The data, derived from 7 randomized clinical trials conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP) since 1958, permit us to conclude that the use of systemic adjuvant therapy is of benefit in both premenopausal and postmenopausal patients with primary breast cancer. Data from the first NSABP trial begun in 1958 with short-course perioperative thiotepa demonstrated a long-term survival benefit in premenopausal but not postmenopausal patients. Ten-year findings from a second trial evaluating response to melphalan (P) implemented in 1972 indicated that, when related to age and nodes, there was a benefit from this drug in both the 1-3 and greater than or equal to 4 positive node premenopausal groups but those with fewer nodes were most improved. In this group characterized by premenopausal women with 1-3 positive nodes, mortality was reduced 64% with a cumulative odds ratio of 3.25 (P = .009) at 10 years after surgery. When related to nuclear grade, there was a striking benefit in survival from P in patients less than or equal to 49 and greater than or equal to 50 years with undifferentiated tumors. The addition of 5-fluorouracil (F) to melphalan (PF) resulted in an increase in disease-free survival and survival over that observed with P in patients less than or equal to 49 and greater than or equal to 50 years of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Role of murine tumor models in cancer treatment research.

Two major factors have contributed to a widely held disenchantment with murine tumor models for drug screening in cancer research: (a) the higher costs of these models in comparison to studies performed with tumor cells in vitro; and (b) the perception that these models have failed to demonstrate satisfactory correlation of chemosensitivity with analogous human tumor types; i.e., murine tumors generally have proved to be sensitive to many more agents than are found to be active in the clinic. The perceived failure of the murine models is discussed with particular reference to the difference in criteria used for evaluating drug sensitivity in murine tumor models versus clinical trials, and we conclude that the perception about murine models is not tenable in light of present information. The very important role of murine tumor models in optimizing dosage and administration schedules and, most importantly, in the development of a new drug to its most useful potential in combination chemotherapy is discussed. The value of this in vivo methodology is stressed.

Animals↗
PubMed1985

Five-year results of a randomized clinical trial comparing total mastectomy and segmental mastectomy with or without radiation in the treatment of breast cancer.

In 1976 we began a randomized trial to evaluate breast conservation by a segmental mastectomy in the treatment of Stage I and II breast tumors less than or equal to 4 cm in size. The operation removes only sufficient tissue to ensure that margins of resected specimens are free of tumor. Women were randomly assigned to total mastectomy, segmental mastectomy alone, or segmental mastectomy followed by breast irradiation. All patients had axillary dissections, and patients with positive nodes received chemotherapy. Life-table estimates based on data from 1843 women indicated that treatment by segmental mastectomy, with or without breast irradiation, resulted in disease-free, distant-disease-free, and overall survival at five years that was no worse than that after total breast removal. In fact, disease-free survival after segmental mastectomy plus radiation was better than disease-free survival after total mastectomy (P = 0.04), and overall survival after segmental mastectomy, with or without radiation, was better than overall survival after total mastectomy (P = 0.07, and 0.06, respectively). A total of 92.3 per cent of women treated with radiation remained free of breast tumor at five years, as compared with 72.1 per cent of those receiving no radiation (P less than 0.001). Among patients with positive nodes 97.9 per cent of women treated with radiation and 63.8 per cent of those receiving no radiation remained tumor-free (P less than 0.001), although both groups received chemotherapy. We conclude that segmental mastectomy, followed by breast irradiation in all patients and adjuvant chemotherapy in women with positive nodes, is appropriate therapy for Stage I and II breast tumors less than or equal to 4 cm, provided that margins of resected specimens are free of tumor.

Breast Neoplasms↗
PubMed1985

Ten-year results of a randomized clinical trial comparing radical mastectomy and total mastectomy with or without radiation.

In 1971 we began a randomized trial to compare alternative local and regional treatments of breast cancer, all of which employ breast removal. Life-table estimates were obtained for 1665 women enrolled in the study for a mean of 126 months. There were no significant differences among three groups of patients with clinically negative axillary nodes, with respect to disease-free survival, distant-disease--free survival, or overall survival (about 57 per cent) at 10 years. The patients were treated by radical mastectomy, total ("simple") mastectomy without axillary dissection but with regional irradiation, or total mastectomy without irradiation plus axillary dissection only if nodes were subsequently positive. Similarly, no differences were observed between patients with clinically positive nodes treated by radical mastectomy or by total mastectomy without axillary dissection but with regional irradiation. Survival at 10 years was about 38 per cent in both groups. Our findings indicate that the location of a breast tumor does not influence the prognosis and that irradiation of internal mammary nodes in patients with inner-quadrant lesions does not improve survival. The data also demonstrate that the results obtained at five years accurately predict the outcome at 10 years. We conclude that the variations of local and regional treatment used in this study are not important in determining survival of patients with breast cancer.

Breast Neoplasms↗
PubMed1985

Tissue mast cells in breast cancer.

The total number of mast cells and the number of such cells observed within and at the periphery of invasive breast cancers from 424 patients enrolled in protocol 4 of the National Surgical Adjuvant Breast Project were correlated with 38 other pathologic and 6 clinical features. High total mast cell counts as well as those within and at the periphery of the cancers were found to be significantly (p less than or equal to .05) associated with a patient age less than 50 years and the degree of tumor lymphoid cell reaction. The latter has also been found to be related to young age and other pathologic characteristics related to mast cell content. This suggests that the mast cells may simply represent another cell type of this reactive change. No differences in 10 year disease-free survival were detected in patients without mast cells and those exhibiting varying numbers of such cells. This information indicates that identifiable mast cells do not represent a prognostic pathologic discriminant in patients with breast cancer. However, this does not unequivocally exclude a role of mast cell secretory products, since only intact and not degranulated or disrupted forms of these cells can be counted.

Actuarial Analysis↗
PubMed1985

Adjuvant therapy in primary breast cancer.

This article considers the role of adjuvant therapy in primary breast cancer, utilizing data from randomized prospective clinical trials as illustrative examples. The ongoing efforts targeted toward addressing some of the unresolved issues are underscored.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Dual role for Escherichia coli RecA protein in SOS mutagenesis.

Induction of the Escherichia coli SOS system increases the ability of the cells to perform DNA repair and mutagenesis. Previous work has shown that this increased mutagenesis is the result of derepression of specific genes through a complex regulatory mechanism controlled by LexA and RecA proteins. One role of RecA protein in this process is to facilitate proteolytic cleavage of LexA protein (the repressor) in response to an inducing signal that reversibly activates RecA protein to perform this function. We show that activated RecA protein plays a second role in SOS mutagenesis, as revealed by analyzing repair of UV-damaged phage lambda in host mutants with alterations in the SOS regulatory system. First, phage mutagenesis was not expressed constitutively in a mutant that is derepressed through lack of functional LexA protein; activated RecA protein was still required. Second, phage mutagenesis was constitutively expressed in the presence of recA mutations that alter RecA protein so that it is activated in normally growing cells. There was also RecA-dependent constitutive expression of SOS mutagenesis in host mutants that lack functional LexA protein and carry plasmids. We discuss several possible biochemical mechanisms for this second role of activated RecA protein in SOS mutagenesis.

Bacterial Proteins↗
PubMed1985

Leukemia in breast cancer patients following adjuvant chemotherapy or postoperative radiation: the NSABP experience.

Since 1971, 8,483 women with primary breast cancer participated in seven trials evaluating adjuvant chemotherapy. Leukemia occurred in only three of 2,068 patients treated by operation alone. The cumulative risk was 0.06% after 10 years in those free of metastases or a second primary tumor, and 0.27% in those with tumor. Thus, leukemia is not an important factor in the natural history of breast cancer. Five of 646 women receiving postoperative regional radiation developed leukemia, an overall risk of 1.39 +/- .49% at 10 years. Twenty-seven cases of leukemia (0.5%) and seven of myeloproliferative syndrome (0.1%) were recorded in 5,299 patients who received L-phenylalanine mustard (L-PAM)-containing regimens. The maximum cumulative risk of leukemia in chemotherapy recipients (leukemia of any type and myeloproliferative syndrome) was 1.68 +/- .33% at 10 years following operation. The risk excluding those with myeloproliferative syndrome was 1.29 +/- .28%. The risk of leukemia in patients free of metastases or a second primary was 1.11 +/- .30% at 10 years, and when combined with myeloproliferative syndrome, it was 1.54 +/- .36%; risks not significantly greater than observed following radiation (P = .58 and .29). No cases of leukemia were observed during the 2 years of chemotherapy and none have occurred after the seventh postoperative year. Comparisons with the surveillance, epidemiology, and end results tumor registries (SEER) data indicate an increased relative risk of acute myelogenous leukemia following postoperative regional radiation (P less than .01) and adjuvant chemotherapy (P less than .001). The findings indicate that hematologic disorders are side effects of both radiation and alkylating agents used in the adjuvant treatment of primary breast cancer. The risk of such events is lower than that reported following treatment of other solid tumors and hematologic malignancies by chemotherapy. The benefit from adjuvant chemotherapy for breast cancer exceeds the risk of leukemia. Since chemotherapy is not uniformly beneficial, efforts should be directed toward identifying responders so that only those who will benefit are exposed to the risk.

Actuarial Analysis↗