Celia J. Menendez-Botet

Estrogen receptor protein of breast cancer as a predictor of recurrence

Estrogen receptor protein (ERP) determinations of primary cancers of 1034 patients with primary breast cancer were done. ERP‐positive patients tended to have a lower recurrence rate and had significantly improved survival. This difference was most apparent in patients with four or more axillary nodes involved. ERP‐positive patients who recurred had a better survival. ERP did not influence response to adjuvant chemotherapy, nor did the presence of progesterone receptor or femtomole level of ERP affect recurrence.

Circulating thymic hormone levels in zinc deficiency

Abstract The effect of zinc deficiency (Zn − ) on the circulating thymic hormone (FTS) levels in A/J mice was studied. After 3 weeks of feeding the mice a Zn − diet, FTS levels were markedly reduced and after 17 weeks, FTS was undetectable. By contrast, the zinc-supplemented (Zn + ) group seemed to maintain FTS levels better than the normal diet group with aging. On the other hand, spleen spontaneous rosette-forming cells (sRFC) were studied for their azathioprine (AZ) sensitivity in A/J mice on different diets. The Zn − mice had fewer sRFC than did the normally fed or Zn + mice. The role of zinc in controlling levels of FTS and thus thymic function is discussed.

Estrogen and progesterone receptors in breast carcinoma: Correlations with epidemiology and pathology

Analysis of estrogen receptor protein (ERP) was carried out on 784 patients with primary breast carcinomas. Significant relationships were found with the following epidemiologic features; age at diagnosis, menstrual status, race, and use of exogenous hormones (contraceptive and menopausal estrogens). Patients taking either type of hormone at diagnosis had lower median total ERP binding levels. Although the data do not explain how recent hormone usage affects tumor ERP, it seems advisable to discontinue these hormones as early as possible before a breast biopsy because they may cause spuriously low ERP levels. Correlation with pathology variables confirmed most prior observations relating to tumor type, histologic grade, and lymphocytic infiltrate. However, in this large series, infiltrating lobular carcinomas were not ERP‐positive more frequently than duct carcinomas to any significant degree. The pattern of progesterone receptors (PRP) did not vary significantly with menstrual status, but in other respects correlations of epidemiologic and pathologic variables were similar for ERP and PRP.

Estrone and estradiol content in human breast tumors: Relationship to estradiol receptors

Abstract We have measured the estradiol receptor content together with the endogenous estrone and estradiol concentrations in human breast tissue cytosols. There was no evidence for a relationship between high estrogen levels and low receptor measurements. Receptor positive tumor cytosols contained a statistically significant greater estradiol concentration than those of receptor negative tumors or of normal tissue. This was confirmed in a study of sixteen pairs of tumor and normal tissue from the same breast in which the estradiol but not estrone concentration of the receptor positive tumors exceeded that of its normal partner. The results indicate that (a) false negative receptor assays due to the presence of endogenous estrogens are not likely; (b) receptor positive tissues retain greater amounts of estradiol than receptor negative tumors.

The value of diagnostic aids in detecting pancreas cancer.

By contract with the National Cancer Institute, the accuracy of diagnostic techniques was assessed in 184 patients suspected of having pancreas cancer. Of 138 patients who were operated upon, 89 were found to have pancreas duct cancer, 30 had cancer of a different site of origin in the head of the pancreas region and in 19 there was no evidence of cancer at operation. All of the 46 patients who were not operated upon, 13 proven to have cancer and 33 patients discharged as free of cancer, were followed in our clinic. The majority of our patients presented with signs and symptoms of biliary obstruction. Computerized transaxial tomography (CTT) gave a “correct” diagnosis in 31 of 33 patients (94%) with proven cancer, there were 2 patients with a false negative report and a false positive diagnosis occurred in 8 of 20 patients (40%) without cancer. Celiac angiography (CA) gave a correct diagnosis in 78 of 94 patients (83%) with cancer, a false negative in 17%, and a false positive in 32%. 75Sele‐nomethionine pancreas scan correctly diagnosed 27 of 36 patients (75%) with cancer, gave a false negative in 25% and a false positive in 31%. Ultrasonog‐raphy gave a correct diagnosis in 18 of 27 patients with cancer (67%), a false negative in 33% and a false positive in 28%. Endoscopic retrograde cholangio‐pancreatography diagnosed correctly 8 of 11 cases (73%) of cancer, there were false negative diagnoses in 3 cases (27%) and false positives in 3 of 14 patients (21%). Duodenal aspiration techniques gave a very low percentage of correct diagnoses. Chronic pancreatitis most commonly gave rise to a false positive diagnosis. Serum alkaline phosphatase was elevated in 82% of patients, gave 18% false negatives and 33% false positives. Carcinoembryonic antigen (CEA) was elevated (> 2.5 ng/ml) in most of the pancreas cancer patients but also in patients with other cancers and with non‐cancerous diseases. In our hands, CTT, CA, alkaline phosphatase, 75Se‐methionine and ultrasonography, in descending order, have given the highest percentage of correct diagnoses but false positive and false negative diagnoses prevented any single test from being conclusive.

Estrogen receptor protein (ERP) in multiple tumor specimens from individual patients with breast cancer.

We have studied 29 patients from whom two or more spatially and temporally separate samples of breast carcinoma were obtained for ERP analysis. Differences in ERP were obtained in 24% of all cases studied. The greatest degree of variation was found when comparing a primary tumor with a subsequent metastasis (38%). Among eight patients with ERP negative (—) primary tumors, six had ERP (—) and two ERP positive (+) metastases. Among 11 patients with ERP (+) primaries eight had ERP (+) and three ERP (‐) metastases. Variations were found in 20% of multiple nonsimultaneous metastases from individual patients. The difference in average interval between cases that did not show variation (9.6 months) and those that did vary (19.3 months) suggests that variation may be more likely to occur with later metastases. However, there was considerable overlap in the range of intervals. These findings underscore the need to biopsy readily accessible recurrences rather than to rely on the results of prior specimens. There was no apparent consistent relationship of these variations to age, site of specimen, interval between specimens or the histologic features of the tissues submitted for analysis. Two patients with an ERP (+) primary tumor had ERP (—) metastases after interval therapy. Similar variations were observed in patients who did not have interval therapy. The data do not permit any definite conclusions as to the effect of chemotherapy or radiation on the ERP properties of mammary carcinoma.

Estrogen receptor protein in lesions of the male breast. A preliminary report

Eleven specimens of breast lesions obtained from 10 male patients were analyzed for estrogen receptor protein (ERP). Three patients (ages 49, 77, 82 years) had infiltrating duct carcinomas with no axillary metastases. ERP in each of these was positive. Eight specimens with gynecomastia, one of which was obtained from the 77‐year‐old patient with carcinoma in the same breast, were also analyzed. Of these ERP was positive in a 59‐year‐old man who had cirrhosis of the liver; two patients with borderline ERP had hepatitis and testicular seminoma, respectively. No relationship between histopathologic features of the lesions and ERP results was found and it is too early to relate these ERP studies to prognosis in these patients. Review of available literature, including our cases, reveals that six of eight male breast carcinomas were ERP‐positive.

Zinc deficiency, depressed thymic hormones, and T lymphocyte dysfunction in patients with hypogammaglobulinemia

Abstract Zinc deficient humans and animals have depressed thymic mass and increased susceptibility to infection. In the present studies, we investigated the relationship between cellular immunity, thymic hormones, and serum zinc levels in 19 patients with common varied immunodeficiency. Five (26%) had serum zinc levels 2 SD below normal and 11 (58%) had abnormally low lymphocyte proliferation to at least one mitogen. A significant statistical correlation between zinc levels and lymphocyte proliferation to phytohemagglutinin and concanavalin A was identified. Forty-two percent had abnormally low levels of facteur thymique serique and 74% had low levels of thymopoietin, although no statistical relationship between the levels of these hormones, zinc levels, or lymphocyte proliferation could be identified. Three patients with the most profound zinc deficiency had substantial increases in thymic hormones after zinc repletion, and two had complete resolution of intractable diarrhea. A therapeutic potential of zinc for certain patients with hypogammaglobulinemia is suggested.

Fatal Thrombocytopenia and Liver Failure Associated with Carboplatin Therapy

A patient with fatal severe thrombocytopenia and acute hepatic necrosis complicating carboplatin (JM8, CBDCA, NSC 241240) therapy is described. The patient, an 18-year-old man with acute lymphocytic leukemia, was given high-dose carboplatin as a part of a phase I trial of this agent for the treatment of leukemia. Carboplatin (270 mg/m2/day) was administered as an intravenous infusion on five consecutive days, and the patient died 10 days after his last dose of carboplatin from complications of thrombocytopenia and acute liver necrosis. Autopsy revealed hemorrhage into the substance of the myocardium and hemorrhagic centrilobular liver necrosis. The temporal relationship between the initial rise in this patients liver function tests and treatment with carboplatin suggests that this patients liver failure was in part due to carboplatin. The autopsy findings of hemorrhage into the substance of the myocardium and centrolobular liver necrosis suggest that, in addition to its direct effects, carboplatin may have also contributed indirectly to this patients liver failure through the complications of thrombocytopenia.

Levels of Estrogen and Progesterone Receptor Proteins in Patients with Breast Cancer During Various Phases of the Menses

Analysis of estrogen and progesterone receptor proteins was carried out in 75 premenopausal and 79 postmenopausal patients with primary operable breast carcinoma who were treated from January 1983 to December 1984. The frequency of estrogen receptor protein positive/progesterone receptor protein positive (+/+); estrogen receptor protein negative/progesterone receptor protein negative (-/-); estrogen receptor protein negative/progesterone receptor protein positive (-/+); and estrogen receptor protein positive/progesterone receptor protein negative (+/-) was 40.5%, 30.5%, 23%, and 6% in premenopausal patients, respectively, and 52%, 24%, 2.5%, and 21.5% in postmenopausal patients, respectively (p less than 0.001). The mean positive estrogen receptor protein concentration (expressed as femtomoles per milligram of protein +/- SEM) was significantly higher in postmenopausal patients (54 +/- 6) than in premenopausal patients (19 +/- 2) (p less than 0.005). The progesterone receptor protein values did not differ significantly between these two groups. The phase of the menstrual cycle was recorded at the time of surgery in the 75 premenopausal women. Maximum receptor positivity occurred in the secretory phase, however, this difference is not statistically significant, and our data suggest that there are no distributional differences between the phase of menses and positivity of estrogen and progesterone receptor proteins. Future studies which included analyses of circulating sex steroid levels and receptor proteins will provide a better understanding of complex hormonal regulatory mechanisms which exist in patients with breast cancer.