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Biomedical subjects

O H Pearson

Publications and source records attributed to O H Pearson.

At least 37 records · Page 2Linked to original sources
PubMed1982

Estrogen receptor status as a prognostic indicator for stage I breast cancer patients.

The prognostic value of estrogen receptor determination was studied for 510 stage I (axillary node negative) breast cancer patients treated by mastectomy alone. Results at 60 months after mastectomy indicate that stage I patients whose tumors lack estrogen receptors fall into a significantly poorer prognostic group for both recurrence and survival than those whose tumors contain estrogen receptors. Within the postmenopausal group, estrogen receptor negative (ER -) patients are recurring more rapidly than estrogen receptor positive (ER +) patients. Within the premenopausal group, ER + patients have a recurrence rate identical to ER - patients, which is apparent only after prolonged follow-up. In contrast to postmenopausal ER + patients, premenopausal ER + patients appear to have no prognostic advantage over the ER - patients, and thus constitute a high risk group for which adjuvant endocrine therapy might prove beneficial.

Breast Neoplasms↗
PubMed1982

Hormone dependency in N-nitrosomethylurea-induced rat mammary tumors.

The majority (87%) of N-nitrosomethylurea-induced rat mammary tumors regressed within 1 week after hypophysectomy (hypox). After a hypox-induced tumor regression, ovine PRL (oPRL), and 17 beta-estradiol (E2) were administered separately or in combination in order to define the individual role of these hormones in regulating tumor growth and influencing estrogen (E), progesterone (Pg), and PRL receptor (R) levels. Administration of E2 (2.5 micrograms twice daily) or oPRL (20 IU daily, started 5 days after hypox and continued for 10 days, resulted in stabilization of tumor growth. Simultaneous administration of E2 and oPRL resulted in a synergistic effect and reactivation of tumor growth. ER levels in mammary tumors were significantly lower than those in the control 15 days after hypox (P less than 0.01). Treatment with E2, oPRL, or both simultaneously had no significant effect on ER levels. A significant decline in PgR levels was noted at both 5 and 15 days after hypox. Whereas treatment with oPRL had no significant effect on PgR levels, E2 administration either alone or in combination with oPRL restored PgR levels to control values. PRLR levels were unchanged from control values at 5 days, but significantly declined (P less than 0.005) 15 days after hypox. Treatment with E2, oPRL, or both hormones simultaneously partially maintained PRLR and prevented the decline to the extremely low level noted in the untreated group. We conclude that the growth of nitrosomethylurea-induced rat mammary tumors is dependent on both E2 and PRL. There was a synergistic effect between E2 and PRL on tumor growth but not on ER, PgR, or PRLR. Neither E2 nor PRL had any significant effect on ER after hypox. PgR is under E2 control. Either E2 or PRL or both hormones were able to maintain PRLR in mammary tumors after hypox.

Adenocarcinoma↗
PubMed1982

Effect of high-dose oestrogen administration on the growth and prolactin receptor content of N-nitrosomethylurea-induced mammary tumours in the rat.

The effect of chronic administration of a high dose of oestradiol benzoate (OB) on growth and prolactin receptor content of the N-nitrosomethylurea (NMU)-induced rat mammary tumour was investigated. Daily i.m. administration of 50 microgram OB for 8 days to tumour-bearing rats induced marked reduction in tumour size which was already significant after only three injections. Simultaneous daily administration of 1 mg perphenazine to stimulate endogenous prolactin release counteracted the inhibitory effect on tumour growth of OB but only partially since the tumours grew significantly more when perphenazine was injected alone. No treatment significantly affected prolactin receptor content in the tumours. We concluded that administration of pharmacological doses of OB has a potent antitumour action on the NMU-induced rat mammary tumour. This effect can only partially be explained by inhibition of the peripheral action of prolactin.

Animals↗
PubMed1982

Role of estrogen and prolactin in the growth and receptor levels of N-nitrosomethylurea-induced rat mammary tumors.

Forty-eight of 81 (59%) of N-nitrosomethylurea-induced rat mammary tumors regressed in average to almost one-half of the original size 10 days after ovariectomy (ovax) (hormone responsive), while 33 remained essentially unchanged (hormone resistant). AT 20 days after ovax, further decline in hormone-responsive tumors was observed when the rats were treated daily with 0.9% NaCl solution on the tenth day after ovax. Treatment for the same length of time with estrogen either alone or in combination with bromocryptine (to effectively suppress serum prolactin level) prevented tumor regression in hormone-responsive tumors. A similar effect was observed when rats were treated with perphenazine (to stimulate endogenous prolactin secretion) either alone or in combination with the antiestrogen tamoxifen. Estrogen receptors (ERs) significantly declined after ovax. Treatment with estrogen or perphenazine did not have any significant effect on ER level. Progesterone receptors (PGRs) became virtually undetectable after ovax. Treatments with estrogen, estrogen plus bromocryptine, and perphenazine plus tamoxifen but not perphenazine alone were able to partially restore PGRs although this effect was of borderline statistical significance. ER and PGR levels were not significantly different between hormone-responsive and -resistant tumors within each group. We conclude that both estrogen and prolactin play a role in the growth of the N-nitrosomethylurea-induced rat mammary tumor. Changes in ER and PGR levels did not correlate with tumor growth under the present experimental conditions.

Animals↗
PubMed1982

Antiestrogen treatment of breast cancer: an overview.

The nonsteroidal antiestrogen tamoxifen has emerged as a highly effective, nontoxic endocrine therapy for women with Stage IV and II estrogen receptor-positive breast cancer. Tamoxifen appears to act by blocking endogenous estrogen action at the target tissue level rather than by suppression of circulating estrogen levels. In a series of 113 consecutive, selected patients with Stage IV breast cancer, tamoxifen induced objective remissions in 50% lasting an average period of 21 + months and a median period of 16 months. These results are comparable to previous results with surgical hypophysectomy. Recent randomized studies comparing pharmacological doses of estrogen versus tamoxifen in postmenopausal women with Stage IV breast cancer have shown comparable results with these two treatment modalities. Antiestrogen therapy has been shown to be effective in some patients after prior endocrine additive therapy and, in particularly, after ablative procedures, such as ovariectomy, adrenalectomy, and hypophysectomy. It has been shown that circulating estrogens are not completely eliminated following ablation of these endocrine glands, which may account for the effectiveness of antiestrogen in this setting. Other endocrine therapies have been shown to be effective after prior treatment with antiestrogen. Hypophysectomy can induced remissions in 60% of patients who initially responded to tamoxifen and in 25% of patients who failed to benefit from tamoxifen. Recent studies have shown that aminoglutethimide plus hydrocortisone may also induce remissions in some patients after prior treatment with tamoxifen. This latter finding is of particular interest since aminoglutethimide is thought to work by blocking estrogen production, and the finding suggests that tamoxifen does not completely block all endogenous estrogen activity. Fluoxymesterone has been shown to induce remissions after tamoxifen or after tamoxifen plus hypophysectomy, and there was no correlation between the response to antiestrogen abd subsequent response to androgen. Because of its effectiveness and minimal side effects, tamoxifen is considered to be an initial endocrine therapy of choice in women with breast cancer. However, it has its limitations, as demonstrated by the results of secondary endocrine therapies such as hypophysectomy, medical adrenalectomy, and androgen therapy.

Adrenalectomy↗
PubMed1981

Androgen-induced remissions after antiestrogen and hypophysectomy in stage IV breast cancer.

Fluoxymesterone (Halotestin), 10 mg p.o. BID, was given to 33 women with Stage IV breast cancer who had previously been treated wih the antiestrogen tamoxifen (Nolvadex) and of whom 17 had also undergone hypophysectomy. Objective remissions were obtained in 13 patients (39%) with an average duration of 11+ months. Response rate to fluoxymesterone was similar in patients who had previously responded to tamoxifen and in those who had failed. Duration of response was longer in the former group (12+ vs. 8 months), but this difference was not statistically significant. Of 17 patients who had been previously treated with tamoxifen and hypophysectomy, seven obtained further remission from fluoxymesterone for an average duration of ten months. Two patients with remissions from fluoxymesterone had previously failed to respond both to antiestrogen therapy and to the removal of the pituitary gland. Androgens appear to be an effective sequential endocrine treatment of Stage IV breast cancer after tamoxifen and hypophysectomy. The mechanism by which androgens induce tumor regression in some patients is probably not an antiestrogenic effect or an indirect effect mediated through the pituitary gland, but perhaps a direct action at the tumor level.

Breast Neoplasms↗
PubMed1981

Sequential endocrine therapy and chemotherapy in metastatic breast cancer: effects on survival.

Follow-up data of 113 patients with stage IV breast cancer treated with the antiestrogen tamoxifen show that the duration of remission is in average in excess of 21 months with a median of 16 months. Survival from start of antiestrogen therapy was significantly longer in patients who responded to tamoxifen, in those with dominant site of disease in the soft tissue, and in those with less extensive metastatic involvement. Overall survival from onset of metastasis was also much longer in patients who had responded to tamoxifen than in those who had failed (median of 52 and a half months vs 23 months). Hypophysectomy and androgen therapy used sequentially after antiestrogen each induced further remissions in almost half of the patients with a median duration of 16 months and 10 months respectively. Five drug chemotherapy used in most patients after maximum benefit had been obtained with endocrine therapy induced remissions in two-thirds of the patients with a median duration of 8 months. Adriamycin used sequentially as a single agent induced significant further palliation in almost half of the patients with a median duration of 4 and a half months. We conclude that sequential endocrine therapy and chemotherapy is highly effective in the treatment of stage IV breast cancer and offers prolonged survival to patients with hormone responsive tumors.

Androgens↗
PubMed1981

Adjuvant therapy of stage II breast cancer: 48-month follow-up of a prospective randomized clinical trial.

A prospective, randomized clinical trial of adjuvant treatment of 318 stage II breast cancer patients, using chemotherapy, the antiestrogen tamoxifen, and immunotherapy is reported at 48 months follow-up. Women whose primary tumors have no estrogen receptors fall into a significantly poorer prognostic group than those whose tumors contain estrogen receptors. None of the adjuvant regimens appeared to offer any clear-cut advantage for the estrogen receptor negative patients. Those women whose primary tumor contains estrogen receptors appear to be in a prognostically favorable group, when their treatment regimen included the antiestrogen, tamoxifen. The adjuvant use of BCG immunotherapy does not appear to offer additional benefit, but the follow-up period of these treated patients is too brief to be conclusive. A longer period of observation is needed to determine whether this systemic treatment in estrogen receptor positive patients is preventing recurrence or merely delaying it.

Antineoplastic Agents↗
PubMed1981

Uterine oestrogen and progesterone receptors in the ovariectomized rat.

The effect was studied of repeated injections of oestradiol-17 beta (5, 10, 25, 50 micrograms) given for various lengths of time (3, 5, 9 days) on total cell content of oestrogen receptors and cytosol progesterone receptors in the uteri of ovariectomized rats. An additional group of rats was injected daily with 50 micrograms oestradiol benzoate (OB) for 9 days in order to achieve a more sustained concentration of oestradiol in the blood. Injections were begun 24h after ovariectomy and the rats were killed 24h after the last injection. Daily administration of 5 micrograms oestradiol prevented the initial transient rise in oestrogen receptors which was observed in the uteri of untreated rats after ovariectomy. Repeated injections of 10 micrograms oestrogen produced an initial lowering in oestrogen receptors after 3 days of treatment which was followed by a prompt rise at 5 and 9 days when treatment was continued. A significant reduction in oestrogen receptors occurred at all times studied when rats were injected daily with 25 and 50 micrograms oestradiol. A more profound reduction in oestrogen receptors was observed in the group of rats treated for 9 days with 50 micrograms OB. Synthesis of progesterone receptors was stimulated by all doses of oestrogen studied. Concentrations of progesterone receptors were significantly higher after 3 and 5 days of treatment with 25 and 50 micrograms oestrogen. After 9 days of treatment, however, concentrations of progesterone receptors were virtually identical in all treated groups, including the group treated with OB. We have concluded that large doses of oestrogen significantly decrease oestrogen receptor content in the rat uterus, especially when OB is used. The degree of reduction, however, is only moderate under these experimental conditions and is insufficient to inhibit synthesis of progesterone receptors.

Animals↗
PubMed1980

Adjuvant chemotherapy, antiestrogen therapy and immunotherapy for stage II breast cancer: 45-month follow-up of a prospective, randomized clinical trial.

The results of adjuvant chemotherapy (CMF), endocrine therapy (t), and immunotherapy (BCG) in 318 women who had undergone mastectomy for Stage II breast cancer are reported after 45 months of life table analysis. CMFT therapy was found to be more effective than CMF alone in increasing recurrence-free survival. This beneficial effect appears to be limited to patients with estrogen receptor-positive tumors (ER+). Patients with estrogen receptor-negative tumors (ER-) (< 3 fmol/mg) have increased recurrence rates and higher mortality.

Antineoplastic Agents↗
PubMed1980

Estrogen and progesterone receptors in the prediction of response of breast cancer to endocrine therapy.

This review presents our experience with the use of estrogen receptors (ER) and progesterone receptors (PgR) in the prediction of response to endocrine therapy in stage IV breast cancer. Presence of ER (> 3 fmol/mg cytosol protein) significantly predicted response to the antiestrogen tamoxifen and to hypophysectomy. ER-negative patients did not respond to either modality of therapy in our series. The absolute amount of ER did not significantly improve our ability to predict response to hormone treatment. In our experience, limited to a small number of patients, the presence of PgR in addition to ER did not increase the probability of response to endocrine therapy. Our findings underscore the usefulness of ER measurement in the prediction of response to either antiestrogen therapy or hypophysectomy in metastatic breast cancer.

Breast Neoplasms↗
PubMed1980

Transsphenoidal microsurgery in the treatment of acromegaly and gigantism.

Twenty-five patients with acromegaly and 3 patients with gigantism underwent transsphenoidal microsurgery in an attempt to remove the tumor and preserve normal pituitary function whenever possible. An adenoma was identified and removed in 27 of 28 patients. Evaluation 3--6 months postoperatively revealed a GH level less than 5 ng/ml in 29 patients, 5--10 ng/ml in 4 patients and 11--29 ng/ml in 4 other patients. Dynamics of GH secretion were normal in 11 patients who had normal pituitary function and are considered cured. Two patients with low or undetectable GH levels are also considered cured at the expense of being hypopituitary. Three of 7 patients with normal basal GH levels but abnormal dynamics of GH secretion relapsed within 1 yr. Eleven of the 13 patients considered cured did not have extrasellar extension, while 14 of the 15 patients not cured had extrasellar extension. Five patients who were not cured with surgery received radiation therapy. Three patients were treated with an ergot derivative, Lergotrile mesylate, after surgery and radiation therapy failed to normalize GH levels. Transsphenoidal microsurgery is an optimal form of therapy for patients with acromegaly or gigantism, especially those with no extrasellar extension. Dynamics of GH secretion are very useful in evaluating the completeness of adenoma removal.

Acromegaly↗
PubMed1980

Pituitary Cushing's disease without adenoma.

Recent reports of patients with Cushing's disease who have been explored via the transsphenoidal route indicate that the great majority has pituitary adenomas. We report a patient with biochemically documented pituitary-based hypercortisolism who had a clinical and biochemical remission following hypophysectomy. Serial sections of the pituitary tissue removed showed hyperplasia of corticotroph cells but no adenoma. Hypophysectomy was complete as documented by serum levels of FSH, LH, TSH, prolactin, hGH and ACTH at the lower limits of the respective assays, with no response to appropriate stimuli. This case demonstrates that a minority of patients with Cushing's disease has corticotroph cell hyperplasia without a pituitary adenoma.

17-Hydroxycorticosteroids↗
PubMed1980

Sequential use of endocrine therapy and chemotherapy for metastatic breast cancer: effects on survival.

One hundred and ten patients with stage IV breast cancer were treated with five-drug chemotherapy consisting of prednisone, cyclophosphamide, 5-fluorouracil, methotrexate, and vincristine. Sixty-four percent of 97 evaluable patients achieved a remission, with a median duration of 9 months. Age, disease-free interval, and menopausal status did not affect response to chemotherapy. Patients with visceral dominant site of disease tended to have a lower response rate compared to those with bone or soft tissue dominant site of disease. Remission rate was similar in hormone-responsive and -resistant tumors, although median duration of remission was longer in the former group (11 versus 9 months; P less than 0.05). Median survival from onset of metastasis was much longer in patients who had responded to previous endocrine therapy than those who had failed (53 versus 23 months; P less than 0.0005). Thirty-four percent of the 59 patients who were subsequently treated with Adriamycin after either relapse or failure with combination chemotherapy obtained further palliation, with a median duration of 4 1/2 months. We conclude that cytotoxic chemotherapy is effective in hormone-responsive and -resistant tumors. Sequential endocrine therapy and chemotherapy offer long-term survival to patients with hormone-responsive tumors.

Adult↗