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R Poisson

Publications and source records attributed to R Poisson.

At least 19 recordsLinked to original sources

Potential role for somatostatin analogues in breast cancer: rationale and description of an ongoing trial.

Somatostatin analogues such as octreotide have been shown in experimental systems to exhibit antineoplastic activity. Further laboratory and clinical research is needed to clarify the mechanism of action of somatostatin analogues as antineoplastics, and to determine if the encouraging preclinical results will lead to novel endocrine approaches to the treatment of breast cancer.

Aminoquinolines

Two months of doxorubicin-cyclophosphamide with and without interval reinduction therapy compared with 6 months of cyclophosphamide, methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifen-nonresponsive tumors: results from the National Surgical Adjuvant Breast and Bowel Project B-15.

The National Surgical Adjuvant Breast and Bowel Project (NSABP) implemented protocol B-15 to compare 2 months of Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) and cyclophosphamide (AC) with 6 months of conventional cyclophosphamide, methotrexate, and fluorouracil (CMF) in patients with breast cancer nonresponsive to tamoxifen (TAM, T). A second aim was to determine whether AC followed in 6 months by intravenous (IV) CMF was more effective than AC without reinduction therapy. Through 3 years of follow-up, findings from 2,194 patients indicate no significant difference in disease-free survival (DFS, P = .5), distant disease-free survival (DDFS, P = .5) or survival (S, P = .8) among the three groups. Since the outcome from AC and CMF was almost identical, the issue arises concerning which regimen is more appropriate for the treatment of breast cancer patients. AC seems preferable since, following total mastectomy, AC was completed on day 63 versus day 154 for conventional CMF; patients visited health professionals three times as often for conventional CMF as for AC; women on AC received therapy on each of 4 days versus on each of 84 days for conventional CMF; and nausea-control medication was given for about 84 days to conventional CMF patients versus for about 12 days to patients on AC. The difference in the amount of alopecia between the two treatment groups was less than anticipated. While alopecia was almost universally observed following AC therapy, 71% of the CMF patients also had hair loss and, in 41%, the loss was greater than 50%. This study and NSABP B-16, which evaluates the worth of AC therapy in TAM-responsive patients, indicate the merit of 2 months of AC therapy for all positive-node breast cancer patients.

Antineoplastic Combined Chemotherapy Protocols

Effects of a rapid antigen test for group A streptococcal pharyngitis on physician prescribing and antibiotic costs.

Decision analysis and opinion survey suggest that introduction of rapid antigen detection tests should decrease the number of patients with negative test results for group A streptococcal pharyngitis treated by antibiotics. We reviewed all cases in which a test for group A streptococcal pharyngitis was performed during the last 7 months of culture diagnosis and the first 7 months of antigen test diagnosis at an inner city community health center, recording culture or antigen test results, whether antibiotics were prescribed, and patient status (as regular health center patients or patients referred to the center). Positive rates for culture and antigen-test periods were similar (10% and 12%), but 53% of patients with negative culture were treated, where only 32% of patients with negative antigen-test results received prescriptions. Significant reductions in the treatment of patients with negative test results were found in both patient-status subpopulations: health center patients, 43% to 29%; referred patients, 91% to 52%. Among health center patients reductions were consistent for both adult (30% to 21%) and child and adolescent (55% to 45%) age groups. For all patients with negative test results, direct costs of diagnostic reagents and antibiotic prescriptions fell from $3.58 per patient with culture to $3.45 with antigen testing; the $0.13 savings per patient was due to less treatment of referred patients. Thus, rapid antigen testing led to (1) significantly fewer patients with negative test results receiving antibiotic prescriptions; and, (2) savings in antibiotic costs offsetting reagent cost of antigen detection diagnosis.

Adolescent

Eight-year results of a randomized clinical trial comparing total mastectomy and lumpectomy with or without irradiation in the treatment of breast cancer.

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.

Breast Neoplasms

A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor-positive tumors.

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.

Adult

Isolation of the human anionic glutathione S-transferase cDNA and the relation of its gene expression to estrogen-receptor content in primary breast cancer.

The development of multidrug resistance in MCF7 human breast cancer cells is associated with overexpression of P-glycoprotein, changes in activities of several detoxication enzymes, and loss of hormone sensitivity and estrogen receptors (ERs). We have cloned the cDNA for one of the drug-detoxifying enzymes overexpressed in multidrug-resistant MCF7 cells (AdrR MCF7), the anionic isozyme of glutathione S-transferase (GST pi). Hybridization with this GST pi cDNA, GST pi-1, demonstrated that increased GST pi activity in AdrR MCF7 cells is associated with overexpression but not with amplification of the gene. We mapped the GST pi gene to human chromosome 11q13 by in situ hybridization. Since multidrug resistance and GST pi overexpression are associated with the loss of ERs in AdrR MCF7 cells, we examined several other breast cancer cell lines that were not selected for drug resistance. In each of these cell lines we found an inverse association between GST pi expression and ER content. We also examined RNA from 21 primary breast cancers and found a similar association between GST pi expression and ER content in vivo. GST pi mRNA content in 11 ER-positive tumors (less than or equal to 10 fmol/mg of protein) was significantly different from the GST pi content of 10 ER-negative tumors (P = 0.002; Mann-Whitney Wilcoxon test for two independent samples). The finding of similar patterns of expression of a drug-detoxifying enzyme and of ERs in vitro as well as in vivo suggests that ER-negative breast cancer cells may have greater protection against antineoplastic agents conferred by GST pi than ER-positive tumors.

Breast Neoplasms

Depression and body image following mastectomy and lumpectomy.

A twenty year debate about the appropriate surgery for breast cancer has resulted in two clinical trials comparing radical vs more conservative operations. Despite the favorable results of these trials, the majority of breast cancer patients in North America still undergo mastectomy. We investigated the psychological and social adjustment following total and partial mastectomy in a group of patients randomly assigned to one or the other operation (National Surgical Adjuvant Breast Protocol--B-06). Total mastectomy patients showed higher levels of depression and less satisfaction with body image. Partial mastectomy patients did not display any measurable increase in fear of recurrence. Patients undergoing radiation therapy showed surprising increase in depressive symptoms. Radiation therapy could well be more frightening to breast surgery patients than had been anticipated. These patients may benefit from some anticipatory counselling.

Body Image

Localization of abnormal parathyroid gland(s) using thallium-201/iodine-123 subtraction scintigraphy in patients with primary hyperparathyroidism.

Tl-201/I-123 subtraction scintigraphy was performed in 17 patients with clinical symptoms and biochemical measurements suggestive of primary hyperparathyroidism. Nineteen abnormal sites were identified. These results were correlated with PTH measurements and surgical findings. Three sites were considered unrelated to the parathyroid glands, two corresponding to palpable thyroid nodules and one to muscle uptake of unknown origin. One scintigram did not reveal either of two abnormal glands while two others were considered falsely positive in view of surgical failure. Fourteen sites corresponded to abnormal parathyroid gland at surgery; five glands, weighing more than 2000 mg, could be correctly located on the Tl-201 scintigraphy prior to the subtraction procedure; six glands, weighing between 500 and 2000 mg, were easily localized after the subtraction procedure; three glands, weighing between 180 and 200 mg, were correctly localized after further manipulation of the subtraction procedure. In a patient with parathyroid hyperplasia, one gland, weighing 150 mg, was not located and another was not found upon surgery. Overall sensitivity was 87.5%. A positive correlation between PTH levels, tumor weight, and ease of detection on scintigraphy was found. This correlation was particularly useful in excluding large abnormal uptake related to thyroid disorder or artifact. The results suggest that Tl-201/I-123 parathyroid scintigraphy could become an alternative to Tl-201/Tc-99m parathyroid scintigraphy, with possibly improved detection of low weight abnormal parathyroid glands.

Adenoma

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

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

Biological markers and breast cancer. A multiparametric study. II. Depressed immune competence.

Immune functions were evaluated in 207 carefully staged breast cancer patients, 54 patients with benign breast diseases and 152 normal controls. All patients were followed for at least five years and the prognostic significance of immune competence determined at diagnosis was established. The parameters employed were dermal hypersensitivity to four skin test antigens and to 2,4-dinitrochlorobenzene (DNCB), blastogenic responses to PHA (phytohemagglutinin), ConA (Concanavalin A), and PW (Pokeweed mitogen) mitogens and percentage of T- and B-lymphocytes. A significant degree of impairment of immune functions was found in breast cancer patients when compared to controls; this was illustrated by depressed T-cell counts and low responses to PHA, ConA and PW mitogens and by depressed responses to recall antigens. However, only lymphocyte stimulation with PHA, percentage of T-cells and dermal hypersensitivity tests showed a continued decrease with advancing stages of the disease. Moreover, among cancer patients with low responses to recall antigens, 61% died before five years, 16% showed progressive disease and only 22% were disease-free after five years of follow-up; compared to 30, 18 and 52%, respectively, in patients with normal responses to recall Ags (overall P value less than or equal to 0.005). A similar relation could be illustrated in patents with low PHA responses as 42% of these patients died before five years, 19% showed progressive disease and 39% were disease-free compared to 26, 19, and 54%, respectively. In patients with normal PHA responses (overall P value less than or equal to .05). It is concluded that initial immunocompetence, determined by parameters of cell-mediated immunity, could be significantly depressed in patients with localized or even premalignant breast disease as well as in advanced cancer. Depressed responses to PHA and dermal hypersensitivity to recall antigens seem to indicate a poorer prognosis. There is no single ideal biological marker as yet. Combined with our previous results on serum proteins, this current study may help us, at the time of initial treatment, in the identification of a subset of Stage I breast cancer patients likely to do poorly.

Adult

Biologic markers and breast cancer: a multiparametric study--1. Increased serum protein levels.

From early 1972 to the end of 1976, the profiles of several serum protein were used to monitor disease stage and prognosis of 207 patients with breast cancer. Six of these proteins, alpha 1-antitrypsin (alpha-AT), alpha 2-ceruloplasmin (Cp), beta 1-transferrin, IgA, C4, and C5, were significantly elevated in these cancer patients and were used as biologic markers in a multiparametric study. Among these breast cancer patients, 72% had at least two of these protein levels elevated, of which alpha-AT (55%), C5 (38%), and IgA (36%) levels were most commonly raised. The number of elevated proteins was parallel to disease progression as 61% (Group 1) and 74% (Group 2) of the patients with operable breast cancer and 90% of patients with metastatic disease showed an elevation of two or more of these nonspecific proteins. There was also a positive correlation between the number of elevated proteins and prognosis; of the 26 patients who died during the five-year follow-up, only four (15%) had no more than one protein level elevated, and 22 (85%) had two or more protein levels elevated. On the other hand, when considered as a group, patients with no or only one protein level elevated had a better prognosis than patients with two or more levels elevated (P less than 0.03). This multiparametric study tends to indicate that the high level of these serum proteins, reflecting an abnormal biochemical profile, provides valuable information that relates to the stage of the disease and patients' prognosis. Results also suggest that these proteins may aid in differentiating the group with high recurrent risks from that with a more favorable prognosis for a given clinical and pathologic stage, illustrating their importance as biologic markers in breast cancer.

Adult

The pituitary-thyroid axis after hemithyroidectomy in euthyroid man.

The pathogenesis of euthyroid goiter is assumed to be TSH dependent, but most studies have not demonstrated elevation of serum TSH. To elucidate the early events involved in thyroid growth, we studied thyroid function in eight euthyroid patients subjected to hemithyroidectomy for solitary cold nodules preoperatively and 2, 15, 60, and 90 days and 36 months, postoperatively. Although within the euthyroid range, serum T4 decreased at 30 days and thereafter up to 90 days (P less than 0.01). Basal serum TSH rose significantly by the 30th day and remained elevated for the entire 90-day period (P less than 0.001). The serum TSH response to TRH was exaggerated from days 15-90 (P less than 0.001). Thirty-six months postoperatively, all parameters of thyroid function were similar to control values, with the exception of one patient who showed an exaggerated response of serum TSH to TRH. We conclude that 1) the dynamic phase of recuperation post hemithyroidectomy is TSH dependent, 2) the serum TSH increase occurs within normal limits and is a temporary event, and 3) 3 yr postoperatively, a new steady state is achieved with normal parameters of thyroid function. Thus, we believe that TSH plays a dominant role in the genesis of goiter.

Adult

Association of endodermal sinus tumour, testicular teratoma and alpha1-fetoprotein.

An endodermal sinus tumour in the retroperitoneal region was associated with the presence of alpha1-fetoprotein (AFP) in the patient's serum. At autopsy a simple cystic teratoma of the right testicle was also found. The association of these two tumours has been reported before. The classification of these malignant germ-cell tumours and an understanding of their evolution may be aided by the discovery that AFP is often found in the patient's serum.

Adult