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Biomedical subjects

O H Pearson

Publications and source records attributed to O H Pearson.

At least 19 recordsLinked to original sources
PubMed1990

Short-term tamoxifen plus chemotherapy: superior results in node-positive breast cancer.

Three hundred eleven patients with node-positive breast cancer were randomized to one of three adjuvant treatments: cyclophosphamide (Cytoxan), methotrexate, and 5-fluorouracil; all of the above with tamoxifen citrate; or all of the above with tamoxifen and bacillus Calmette-Guerin vaccination. Local therapy for all patients was a modified radical mastectomy. Estrogen receptors were measured on all primary tumors. Patients were stratified by the number of positive nodes (one to three nodes and more than three nodes) and estrogen-receptor value (less than 3 femtomole/mg and greater than or equal to 3 femtomole/mg). Follow-up is available, with a mean of 9.1 and maximum of 14.2 years. In this study the efficacy of short-term tamoxifen is apparent over that of chemoimmunotherapy alone and continues to be significant with prolonged follow-up. The addition of tamoxifen to chemoimmunotherapy significantly prolonged disease-free survival among patients with estrogen receptor-positive tumors who were postmenopausal, who had larger tumors (greater than 3 cm), or who had more extensive axillary node involvement (more than three nodes). Tamoxifen improved overall survival for patients with estrogen receptor-positive tumors larger than 3 cm. The addition of bacillus Calmette-Guerin Cytoxan, methotrexate, 5-fluorouracil, and tamoxifen did not significantly alter disease-free or overall survival.

Antineoplastic Agents↗
PubMed1989

Endocrine versus endocrine plus five-drug chemotherapy in postmenopausal women with stage II estrogen receptor-positive breast cancer.

Postmenopausal women who underwent modified radical mastectomy for Stage II, estrogen receptor (ER)-positive breast cancer were randomized to receive endocrine treatment (tamoxifen [T], 40 mg daily for 3 years) alone versus endocrine treatment plus five-drug chemotherapy (Cytoxan [cyclophosphamide, C], methotrexate [M], 5-fluorouracil [F], vincristine [V], and prednisone [P], CMFVP, for 1 year). Chemotherapy consisted of oral P (1 month), oral C (12 months), and intravenous MFV weekly for the first 3 months, biweekly for 3 months, and triweekly for 6 months. Patients were entered into the study from October 1979, to October 1985, and the median follow-up is 55 months. Results show that with 94 postmenopausal women, disease-free survival (DFS) is significantly greater (P = 0.04, log-rank test; P = 0.03, multivariate analysis) in patients receiving CMFVPT as compared to those receiving T alone. These results suggest that intensive chemotherapy combined with T is more effective in delaying recurrence than T alone in postmenopausal patients.

Aged↗
PubMed1987

Recurrence patterns in a prospective study of patients with stage II breast cancer treated with endocrine-chemotherapy.

Local-regional versus distant recurrence patterns were investigated for 311 patients with stage II node-positive breast cancer who were part of an endocrine-chemotherapy adjuvant breast cancer trial. After mastectomy patients were randomized to receive either cytoxan, methotrexate, and 5-fluorouracil (CMF) (1 year) or CMF with tamoxifen (1 year) with or without bacillus Calmette-Guérin (BCG). With a median follow-up of 92.1 months, 55.3% of the patients had recurrences. The first site of recurrence was local-regional for 31.4% of patients and distant for 68.6%. This pattern of first recurrence was not associated with treatment groups, menopausal status, race, estrogen receptor value, number of positive lymph nodes, or tumour diameter. Although patients with a first local-regional recurrence had a better overall prognosis compared with those with a first distant recurrence, 52.2% of those patients with an initial local-regional recurrence developed a distant recurrence within 12 months. Among patients who had a recurrence, 48.3% had a local-regional recurrence at some time during their follow-up. Conclusions from this study are (1) patterns of recurrence were not affected by the addition of antiestrogen therapy to chemotherapy; (2) for the variables tested, including number of positive nodes and tumor diameter, no association with recurrence patterns was found; and (3) most patients (52.2%) with a first local-regional recurrence will develop a distant recurrence within 1 year.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Assessment of tamoxifen as adjuvant therapy in stage II breast cancer: a long-term follow-up.

Results of a prospective, randomized clinical trial of three treatment regimens--cyclophosphamide, methotrexate, and 5-fluorouracil (C); C plus the antiestrogen, tamoxifen citrate (CT); and CT plus bacillus Calmette-Guerin (CTBCG)--in 311 women with stage II breast cancer are reported. The data were analyzed by univariate (product limit and log rank) analysis and by multivariate analysis. Estrogen receptors were measured in all primary tumors. The mean follow-up period was 78.2 months. The regimens containing tamoxifen citrate significantly decreased the risk of recurrence in patients with positive estrogen receptors. The addition of tamoxifen does not, however, appear to provide an advantage in overall survival. No benefit in disease-free or overall survival was observed resulting from the addition of BCG to the treatment regimen. The design of the study did not permit an evaluation of the efficacy of the chemotherapy used inasmuch as all patients received it.

Analysis of Variance↗
PubMed1986

Gradual recovery of lactotroph responsiveness to dynamic stimulation following surgical removal of prolactinomas: long-term follow-up studies.

Prolactin-secreting pituitary adenomas were selectively removed through a transsphenoidal approach from 120 women. Basal serum PRL levels (measured one to six months after surgery) were normal in 96 patients and decreased appreciably but not to normal in the remaining 24 patients. Dynamics of PRL secretion were studied at three to four months in 81 patients who had normal basal PRL level. Two different patterns of response to provocative stimuli were noted in these patients. In one group (group I, n = 65), patients had greater than 100% rise in serum PRL following TRH or perphenazine (Pz) administration. However, when analyzed as a group, the mean +/- SEM incremental responses (delta PRL) to TRH and Pz in these patients (29.9 +/- 1.9, 20.4 +/- 1.5 ng/mL) were significantly less (P less than 0.005 and P less than 0.001) than those of normal women (38.8 +/- 5, 33 +/- 5 ng/mL, respectively). Nineteen of these patients were restudied 12 to 72 months after surgery. The responses to provocative stimulation at that time were improved and similar to normal women. In contrast, in the second group (n = 16) of patients (group II), the responses to stimulation with the same agents were blunted or absent and remained so during subsequent studies. Recurrence of the hyperprolactinemia was noted in 11 of the 16 patients in group II and in only two of 65 patients in group I. The daily serum PRL levels in the immediate postoperative period were higher in patients from group II than those from group I. We conclude that transsphenoidal surgery is an optimal form of therapy for patients with PRL-secreting adenomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1986

Influence of tamoxifen and estradiol on the growth of human breast cancer cells in vitro.

Cells obtained from freshly resected human breast cancer were grown in vitro utilizing the soft agar technique. The effects of adding an antiestrogen (tamoxifen, TAM) and 17 beta-estradiol alone or simultaneously on cell growth were assessed. The addition of TAM (10(-6) M) to the medium resulted in a significant decrease in cell growth in 26 of 36 (72%) estrogen receptor (ER)-positive tumors and in one of 5 ER-negative tumors (20%). The degree of inhibition caused by TAM was significantly higher in the ER-positive tumors that also contain the progesterone receptor (PgR) as compared to those that lacked that receptor (i.e., PgR negative) (46.2 +/- 2% versus 36.2 +/- 1.2% inhibition, P less than 0.01). The simultaneous addition of 17 beta-estradiol (10(-8) M) neutralized the inhibitory effect of TAM (10(-6) M) in the majority of tumors. With the presence of serum in the medium, the addition of 17 beta-estradiol alone resulted in an enhancement of cell growth in 6 of 17 tumors. However, because of the confounding effects of serum in the medium, we studied the individual effect of 17 beta-estradiol (10(-8) M) when added alone under serum-free conditions. Of 20 tumors studied, 17 beta-estradiol significantly enhanced cell growth in 12. There was a 67.8 +/- 12.6% increase in the number of colonies formed in these 12 responding tumors. One of these 12 responding tumors was ER negative as well as PgR negative, while the rest were all ER positive. These in vitro studies demonstrate that this approach can provide valuable information on endocrine mechanisms controlling the growth of human breast cancer.

Breast Neoplasms↗
PubMed1986

The interaction of estrogen receptor status and race in predicting prognosis for stage I breast cancer patients.

As part of a multi-institutional breast cancer data base, 501 stage I, node negative patients have been followed prospectively with a median of 89 months. Patients were treated by a modified radical mastectomy without postoperative therapy. Estrogen receptor (ER) content of the primary tumor was determined in all cases. For the entire patient group at 10 years, the disease-free survival (DFS) rate is 72% and the overall survival (OS) rate is 85%. Both ER value and race (black versus white) were found to be significant prognostic variables for DFS (p = 0.008 and 0.02, respectively) and for OS (p = 0.0001 and 0.01, respectively). ER positive patients had a better DFS and OS rate compared with ER negative patients (74% versus 66% and 90% versus 68%, respectively). Black patients had significantly worse DFS and OS rates compared with white patients (64% versus 74% and 75% versus 86%, respectively). Statistical interaction between the ER and race variables was apparent when comparing the similar DFS for ER positive white (75%), ER negative white (72%), and ER positive black (73%) patients in contrast to a DFS of less than 42% at 10 years for the ER negative black patients. An analysis of the data for the ER negative black patients suggested that the postmenopausal ER negative black patients are at particularly high risk of recurrence and death from breast cancer.

Breast Neoplasms↗
PubMed1985

Adjuvant endocrine therapy, cytotoxic chemotherapy and immunotherapy in stage II breast cancer: 6-year result.

Six-year results of a prospective, randomized clinical trial of three treatment regimens [(1) cytoxan, methotrexate and 5-fluorouracil (CMF); (2) CMF plus the antiestrogen drug, tamoxifen (CMFT); (3) CMFT plus Bacillus Calmette-Guerin (BCG) vaccinations] in 312 women with stage II breast cancer are reported. Addition of tamoxifen to CMF therapy significantly decreased the number of recurrences at 6 years in ER + patients with greater than or equal to 4 positive axillary lymph nodes, and in those with tumor diameter in excess of 3 cm. The beneficial effect of tamoxifen appeared to be independent of the menopausal status. Addition of tamoxifen to CMF had no effect on disease-free survival in ER + patients with 1-3 positive axillary lymph nodes or in patients with ER--tumors. Addition of BCG vaccinations had no discernible effect on disease-free survival. ER measurements in the primary tumor provide important prognostic information regardless of treatment, with ER + patients having increased overall survival after 6 years. Further follow-up is needed to determine whether tamoxifen is delaying recurrence or preventing it in a subset of these patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Growth potential of human uterine leiomyomas: some in vitro observations and their implications.

Tissue culture techniques commonly applied to the study of human vascular smooth muscle were used to evaluate in vitro survival and proliferation of normal and neoplastic human myometrial cells. Despite their growth advantage in vivo, leiomyoma cells displayed a growth disadvantage in vitro compared with normal myometrium from the same patient. Hormonal supplementation with alpha-estradiol, progesterone, and insulin-stimulated myometrial proliferation, whereas beta-estradiol appeared ineffective at the doses tested. Hormonal supplementation also stimulated leiomyoma proliferation in vitro, but there appeared to be heterogeneity in hormonal responsiveness. Heterogeneity in the host hormonal milieu and in the ability of uterine leiomyomas to respond to various hormones may be important factors contributing to the wide variation in growth potential observed in leiomyomas.

Adult↗
PubMed1979

Antihormone treatment of stage IV breast cancer.

The antiestrogen Tamoxifen (T), given orally to 113 patients with stage IV breast cancer, induced objective remission in 50%. Duration of remission in the first 39 patients, with minimum 27 months follow up, is 18 + months; these results are equal to those of surgical hypophysectomy. T prolonged survival in responders. Older age, previous response to endocrine therapy and positive estrogen receptors predicted response to T. T was effective in hypophysectomized patients in whom serum growth hormone and prolactin were undetectable, but serum ostrogens were present in low amount, suggesting a direct stimulatory effect of estrogens at the tumor level. Hypophysectomy induced further palliation after treatment with T, indicating that pituitary hormones may also play a role in the growth of some human breast cancers. Side effects from T were minimal. T is the initial treatment of choice for postmenopausal women with hormone responsive stage IV breast cancer.

Breast Neoplasms↗
PubMed1979

Transsphenoidal hypophysectomy in breast cancer: evidence for an individual role of pituitary and gonadal hormones in supporting tumor growth.

Transsphenoidal hypophysectomy was performed in 212 consecutive patients with metastatic breast cancer: 11 died within 30 days, two of surgical complications and nine of advanced metastatic disease. Two patients were unevaluable because of inadequate follow-up in one and simultaneous radiation treatment in the other. Of 199 evaluable patients 42% had an objective remission. Duration of remission averaged 18+ months with 10 out of 84 patients still in remission. Presence of estrogen receptors in the tumor significantly predicted response to hypophysectomy. Of 156 patients in whom completeness of hypophysectomy was assessed, 128 were thought to have a complete removal as shown by the fact that their growth hormone and prolactin were undetectable after stimulation with arginine or chlorpromazine, respectively. Of 26 patients in whom TRH test was performed, TSH and prolactin were undetectable in 20. Of 23 patients where autopsy was performed only six had microscopic pituitary tissue remaining. Hypophysectomy induced remission in eight of 15 patients who had previously responded and then relapsed to the antiestrogen Tamoxifen and in four of 17 who had failed. Conversely, antiestrogen therapy induced remission in six of 26 patients who had previously responded to hypophysectomy and in whom serum estrogens were present in small amount. These data indicate that both gonadal and pituitary hormones play a role in the growth of some human breast cancers.

Adult↗
PubMed1978

Hypophysectomy for stage IV breast cancer.

Transnasal, transsphenoidal microsurgical hypophysectomy is a useful therapeutic procedure for patients with Stage IV breast cancer which can be peformed in selected patients with minimal morbidity and mortality. Functionally complete hypophysectomy can be accomplished with regularity, and anything less than this is considered to be a technical failure despite the fact that remissions may occur after incomplete hypophysectomy. In view of the recent outstanding results with antiestrogen therapy in patients with breast cancer, we recommend this as the initial treatment in those patients who are good candidates for endocrine therapy. Hypophysectomy has been shown to induce improvement after antiestrogen treatment, particularly in those patients who have had an initial response to antiestrogens as well as in a few patients who failed to benefit. Estrogen receptor measurements in the tumor tissue have been shown to be useful in selecting patients for hypophysectomy as well as for antiestrogen therapy. Prolactin receptors have been found in about 50 per cent of human breast cancers, and their potential usefulness in selecting patients for hypophysectomy is being explored. Hypophysectomy is a definitive therapeutic procedure that should not be used as a last resort in the terminally ill patient.

Adrenalectomy↗
PubMed1978

Prolactin induces its own receptors in rat liver.

Attempts to restore PRL receptors (PRL-R) in liver membranes of hypophysectomized rats with injections of PRL have so far been only partly successful. In the present study, bovine PRL (bPRL) was mixed with polyvinylpyrrolidone (PVP) in order to sustain PRL blood levels with a single injection a day. PRL-R were measured by displacement of the binding of [125I]ovine PRL (lactoperoxidase oxidation) to a 5000 x g particulate fraction of liver by unlabeled ovine PRL. The number of binding sites was calculated by Scatchard analysis and expressed as femtomoles per mg protein. PRL-R were 85 +/- 12 fmol/mg in normal intact female rats. Seven days posthypophysectomy, PRL-R were undetectable. Daily injections of bPRL with PVP for 10 days fully restored PRL-R (117 +/- 32 fmol/mg). No significant change in PRL-R was noted when bPRL was injected with bovine GH (bGH; 120 +/- 23 fmol/mg), bovine LH (bLH; 84 +/- 14 fmol/mg), bGH plus bLH (90 +/- 12 fmol/mg), or estrogens (79 +/- 12 fmol/mg). Daily injections of bGH or bLH, alone or in combination, or estrogens with PVP failed to restore PRL-R. These results demonstrate a direct role of PRL in stimulating the production of its own receptors when a sustained blood level of the hormone is achieved.

Animals↗
PubMed1978

Pituitary function after removal of pituitary microadenomas in Cushing's disease.

Pituitary function has been studied sequentially after transsphenoidal removal of pituitary microadenomas in two men with Cushing's disease. Patient 1 gradually regained normal glucocorticoid levels with normal diurnal variation, metyrapone responsiveness, and low dose dexamethasone suppressibility (17-hydroxycorticosteroid, 6.5-0.9 mg/24 h). GH levels rose from 1 to 35 ng/ml during insulin hypoglycemia and from 2.3 to 27 ng/ml during arginine infusion. PRL secretion rose normally in response to thorazine, and gonadotropin and TSH levels remained normal. Patient 2 regained significant metyrapone responsiveness by 9 months postoperatively (11-deoxycortisol rose to 11.7 micrograms/dl), had a normal spontaneous nocturnal rise in PRL secretion, and normal levels of testosterone and thyroid hormones. The return to normal of cortisol-ACTH dynamics and GH responsiveness in Patient 1 and the normal nocturnal surge in PRL secretion in Patient 2 imply that in these patients the etiology of Cushing's disease was not related to hypothalamic dysfunction.

17-Ketosteroids↗
PubMed1978

Role of pituitary hormones in the growth of human breast cancer.

Hypophysectomy was performed in 28 women with Stage IV breast cancer who were treated initially with antiestrogens. Six of 13 patients who responded to tamoxifen and 2 of 12 who failed to benefit from tamoxifen obtained remissions from hypophysectomy. The remissions average 11+ months. Three of 8 patients treated initially with antiestrogens have responded to androgen therapy. The results suggest that hormones other than estrogen, which appears to play a major role, may be involved in stimulating the growth of some human breast cancers. Prolactin receptors were detectable in 51% of human breast cancers and were detected in both estrogen receptor-positive and -negative tumors. Preliminary clinical correlations suggest that prolactin receptors will not be useful in predicting response to antiestrogen therapy.

Breast Neoplasms↗