Showing papers on "Cancer published in 1980"

The value of estrogen and progesterone receptors in the treatment of breast cancer

Abstract: The estrogen receptor (ER) assay has become a standard practice in the management of advanced breast cancer. Tumors lacking ER respond infrequently to endocrine therapy, whereas response rates of 50 to 60 percent are observed in ER+ tumors. Recent studies indicate that the ER status of the primary tumor is a good predictor of the endocrine dependence of metastatic tumors at the time of clinical relapse. Furthermore, the absence of ER in the primary tumor is an important independent prognostic indicator of higher rate of recurrence and shorter survival. Quantitative analysis of Er and an assay for progesterone receptor (PgR) are two methods for increasing the accuracy of selecting or rejecting patients for hormonal therapy; tumors with a high quantitative ER content or those with a positive PgR display the highest objective response rates. Preliminary analysis suggests that the presence of PgR may be a better marker of tumor hormone dependence than quantitative ER.

Research on Esophageal Cancer in China: a Review

Abstract: Research on esophageal cancer in the People's Republic of China is reviewed. Massive epidemiological studies revealed the prevalence of this disease in China, especially in the Taihang Mountain range areas in the north. Gullet cancer in chickens was also observed in the high-incidence area of Linxian in Henan, suggesting the presence of cancer-causing substances in the environment. Research on the etiology of this cancer has been pursued extensively. Moldy food and pickled vegetables were shown to contain carcinogens. In chemical etiology, nitrosamines and their precursors have received the most attention. The possible roles of trace element deficiencies in the soil, nutritional deficiencies, fungal infection, polycyclic hydrocarbons, and other factors in contributing to the high cancer incidence have been studied. The esophageal cancer problem has also been investigated at the cellular and immunological levels. Mass cytological surveys allowed many cases of early cancer to be detected and treated. Precancerous changes and the use of interventive therapy have been studied in animal models and patients. Prevention, early detection, and early treatment of this cancer have been pursued vigorously in many areas of China.

Leukocyte Interferon-Induced Tumor Regression in Human Metastatic Breast Cancer, Multiple Myeloma, and Malignant Lymphoma

Abstract: Thirty-eight patients with advanced breast cancer, multiple myeloma, and malignant lymphoma were treated with partially purified (about 0.1%) leukocyte interferon. Patients were treated with a remission-induction schedule of 3 million to 9 million antiviral units daily intramuscularly for 4 to 26 weeks. Responding patients were maintained on a schedule of 3 million U three times weekly. Tumor regression was observed in seven of 17 patients with breast cancer. Six of 10 patients with multiple myeloma responded with a decrease of at least 50% in serum myeloma protein levels or Bence Jones protein excretion. Six of the 11 lymphoma patients achieved tumor regression. Complete remissions occurred in two patients. Of the 19 responding patients, five remain on study for 52 to 63 weeks. Toxicity included low-grade fever, fatigue, anorexia, and partial alopecia. Myelosuppression (lowest median leukocyte count, 2500/mm3; granulocytes, 1300/mm3) occurred in most patients. On the basis of this pilot study, we conclude that leukocyte interferon can induce tumor regression in patients with advanced cancer.

Management of Cancer Pain

Abstract: Although pain is generally considered a common accompaniment to cancer, particularly as metastases develop, the actual incidence of cancer-induced pain is relatively uncommon, and resistance to analgesic therapy is rare. Osier reviewed an extensive group of patients with terminal cancer and found that less than 10 percent required analgesia in the preterminal phase of the disease.

Prostaglandin in Human Breast Cancer: Evidence Suggesting That an Elevated Prostaglandin Production Is a Marker of High Metastatic Potential for Neoplastic Cells

Abstract: Prostaglandin (PG) production by human breast cancers was investigated in 91 lesions selected so that the distribution of histologic type was similar to that of the general population of mammary carcinomas. With regard to the shape characteristics of the tumors, PG production was higher in lesions classified T1 and T2 than in lesions classified T3 and T4 (T-classification is based on extent of tumor as graded by the International Union Against Cancer), higher in tumors exhibiting a high cellularity than in lesions with a low tumor cell density and higher in tumors in which the cells were still adherent to each other. A high PG production was associated with the presence of neoplastic cells in tumor lymphatic and blood vessels and in axillary lymph nodes. PG production by node metastases was always higher than that by the primary tumor sites. The analysis of the stroma reaction and the presence of edema and necrosis suggest that an active PG synthesis occurred in lesions in which the tumor cell-surrounding stroma presented characteristics of low resistance to invasive growth of cancer cells. With regard to histologic differentiation and histoprognostic grade of lesions, PG production was elevated in carcinomas that retained a minute part of the acinoductal differentiation and in tumors with a moderate or high degree of cancer. A lesion containing a steroid receptor (SR) tended to produce less PG than did an SR-negative tumor. PG production increased slightly according to ages and times of menopause of the patients. PG production occurred early in the natural course of breast cancer and was elevated in tumors at a time when active tumor invasion proceeded. By contrast, PG production decreased later in the course of tumor development. These results indicated that elevated PG production can be used as a marker of high metastatic potential for neoplastic cells in breast cancer.

Laboratory and Clinical Research in Breast Cancer—A Personal Adventure: The David A. Karnofsky Memorial Lecture

Abstract: This report highlights the series of laboratory and clinical investigations conducted by us during the past quarter of a century which have resulted in the replacement of old concepts of tumor biology with others that have been instrumental in altering the therapy of primary breast cancer. The results of our studies prior to 1968, directed toward a better understanding of metastatic mechanisms, dispelled many of the popularly held hypotheses regarding tumor cell dissemination. They led us to conclude that (a) regional lymph nodes do not trap disseminated tumor cells, (b) there is no orderly pattern of tumor cell dissemination based upon temporal and mechanical considerations, (c) patterns of tumor spread are not solely dictated by anatomical considerations but are influenced by intrinsic factors in tumor cells as well as in the organs to which they gain access, and (d) regional lymph node cells are capable of destroying tumor cells. Negative nodes are the result of the latter and/or because tumor cells traverse nodes rather than that a tumor had been removed prior to dissemination of its cells. The positive lymph node reflects a host-tumor relationship which permits development of metastases rather than that it is an instigator of distant disease. Additional studies have provided ample evidence to indicate that regional lymph nodes are of biological rather than anatomical importance in cancer. They also indicated that it is likely that a tumor (breast cancer) is a systemic disease from its inception. Concomitant with the laboratory studies, a series of “first-generation” breast cancer clinical trials provided evidence concordant with findings from the former. As a result, there emerged a hypothesis alternative to that upon which the primary management of solid tumors has been based for almost 100 years, i.e., the principles of Halsted. The opportunity to test the “alternative” hypothesis became available via a second-generation breast cancer clinical trial begun in 1971. Findings from that trial have important biological implications and provide additional support for the various components of the alternative hypothesis. Increasing evidence emphasizes the heterogeneity of human breast cancers. To continue to consider such tumors as representative of a single disease is inappropriate. It has been demonstrated by us that tumor heterogeneity is not merely an interesting biological observation but that it possesses therapeutic significance as well. The results from three clinical trials indicate that, just as there is heterogeneity between and within primary tumors, so are metastatic microfoci dissimilar and so is their response to chemotherapy disparate. Our observations that patients with putatively greater tumor burdens may be better responders and that increasing the number of drugs may not necessarily improve results are inconsistent with current concepts which provide the basis for the use of adjuvant chemotherapy and suggest that they require reappraisal. The findings indicate that metastatic cellular heterogeneity is an important factor to be considered when assessing therapeutic response. Failure of all populations of patients to respond uniformly to therapy provides a different perspective for assessment of the use of adjuvant therapy. A chemotherapeutic agent, or a combination of agents, can be used as a “probe” to identify subpopulations of patients whose metastases contain cells with common or differing biological properties. A probe capable of defining responders and nonresponders to the therapy used provides direction to the next stage of investigation, determination of the reason for the difference of response. With such information, patients can be selected for a particular therapy. There then appears a rationality to the seemingly irrational use of chemotherapy regimens in the myriad of clinical trials being carried out. An alternative approach is to define in the laboratory the variable biological characteristics of tumor cells, which then permits the choice of therapeutic agents that affect cells possessing that discriminant. The two research approaches, i.e., the use of therapy as a probe and the elucidation of biological information regarding tumor cells, are not exclusive of each other. They are so intertwined that each provides an impetus to the other. There is reason for cautious optimism relative to the curing of more patients with breast cancer in the near future. This will come about because of the use of therapy based upon biological considerations rather than empiricism. Patients will be subsetted according to tumor-host biological properties rather than to clinical manifestations of the disease. Clinical staging as we now know it is apt to become obsolete. It cannot be too strongly emphasized that advances in breast cancer therapy are, short of luck, likely to result only from a better understanding of the biology of the disease. Only by application of the scientific method in both the laboratory and the clinic, as is exemplified by this report, is this likely to come about.

5-Fluorouracil, Doxorubicin, and Mitomycin (FAM) Combination Chemotherapy for Advanced Gastric Cancer

Abstract: Sixty-two patients with advanced measurable gastric cancer were treated with a combination chemotherapy program of 5-fluorouracil, doxorubicin, and mitomycin (FAM). Forty-two percent of patients achieved an objective partial response. The median duration of remission was 9 months and the median survival for responding patients, 12.5 months. The median survival for nonresponding patients was 3.5 months; all patients were dead by 8 months after initiation of therapy. The median survival of all 62 patients treated with FAM was 5.5 months. An analysis of possible prognostic variables including initial performance status, resectability of the primary gastric tumor, and histologic differentiation of the neoplasm failed to account for differences in patient response and survival. The FAM regimen was well tolerated, producing only moderate bone marrow suppression. These results show that patients with metastatic gastric cancer can be effectively palliated with FAM chemotherapy. The efficacy of this regimen should now be tested in patients with less advanced stages of this disease.

Cryptogenic fibrosing alveolitis and lung cancer.

Abstract: Lung cancer was found in 20 (9.8%) of 205 patients with cryptogenic fibrosing alveolitis (CFA) or 12.9% of the 155 patients in this series followed to death. An excess relative risk of lung cancer of 14.1 was found in patients with CFA compared to the general population of comparable age and sex, allowing for the lengths of follow-up of the CFA patients. The relative risk for male smokers was (observed/expected) 15+1.06 = 14.2, and for female smokers (O/E) 2/0.3 = 6.7. Only one male and one female non-smoker had lung cancer. These data suggest that there is an excess risk of lung cancer not wholly accounted for by age, sex, or smoking habit. The distribution of histological types was not obviously different from that found in lung cancer without pulmonary fibrosis. Large opacities suggestive of lung cancer were present at the time of first hospital attendance for symptoms relating to CFA in four of the 20 patients. Finger clubbing was present in 19 (95%) compared with 116/185 (63%) of those so far not developing cancer. There were no other clinical differences at presentation. In particular, cancer was not found especially in those with longer survival from the onset of symptoms of CFA or with a greater initial radiographic change.

Malignancy in Crohn’s Disease

Abstract: Cancer morbidity has been evaluated in a series of 513 patients with Crohn's disease under long-term review between 1944-76. In comparison with morbidity rates for cancer in the West Midlands Region (the geographical area from which these patients were drawn) the 31 tumours that occurred represented a relative risk of 1.7 (P less than 0.01) of cancer at all sites. For tumours at sites within the digestive system the relative risk was 3.3 (P less than 0.001). A significant excess of tumours was found in both the upper (P less than 0.01) and lower (P less than 0.001) gastrointestinal tract. There was no excess of tumours at any site outside the digestive system.

Quantitation of Prostate-specific Antigen in Serum by a Sensitive Enzyme Immunoassay

Abstract: A sensitive sandwich-type enzyme immunoassay has been developed for quantitation of a human prostate-specific antigen (PA). With this method, PA at a concentration as low as 0.10 ng/ml can be detected. The assay was reproducible as within and between assays yielded a coefficient of variation of 5.7% and 4.6%, respectively. Only human prostate tissues ( n = 31) were shown to contain PA. No PA was detected in other human normal or tumor tissues ( n = 13). PA was not detectable in sera from normal females ( n = 17) or female cancer patients ( n = 25). A mean ± S.D. of 0.47 ± 0.661 ng/ml (ranging from less than 0.10 to 2.6) was obtained from a group of 51 normal males. Sera from male patients with nonprostatic cancer contained a similar range of PA as that of normal males. Patients with prostate cancer (371 of 442) and benign prostatic hypertrophy (13 of 19) were shown to have elevated levels of circulating PA. Although no quantitative difference in PA levels was found between the benign prostatic hypertrophy group and Stage A of prostatic cancer, patients with Stages C and D prostatic cancer exhibited significantly elevated levels of PA qualitatively and quantitatively. These results therefore indicate that PA is a histiotypic product of the prostate and may be of use as an adjunctive tool in diagnostic procedures of prostate cancer.

A case-control study of diet and colo-rectal cancer.

Abstract: A case-control study of cancer of the colon and rectum has been conducted in Calgary, Alberta and Toronto, Ontario, Canada. A total of 348 cases of cancer of the colon and 194 cases of cancer of the rectum were individually matched by age, sex and neighbourhood of residence to 542 population controls and frequency matched to 535 hospital controls who had undergone an abdominal operation. Each subject received a personal medical history questionnaire and a quantitative diet history questionnaire. Data on a number of potential non-nutrient risk factors for bowel cancer and on the consumption of 9 nutrients in the 2-month period up to 6 months before interview were analysed. The dietary data thus refer to recent diet consumed in a period antedating the diagnosis of, and in most cases symptoms from, large-bowel cancer in the cases, and a corresponding time period in the controls. The major findings were an elevated risk for those with a history of bowel polyps, and for those with an elevated intake of calories, total fat, total protein, saturated fat, oleic acid and cholesterol. No association was seen with an elevated intake of crude fibre, Vitamin C and linoleic acid. The nutrients for which an increased risk was demonstrated were highly correlated, though multivariate analysis using logistic regression indicated highest risk for saturated fat, with evidence of a dose-response relationship. The findings in both cancer sites, both sexes and with both sets of controls were quantitatively very similar. The population-attributable risk for colon and rectal cancer combined was estimated from the neighbourhood controls to be 41% for males and 44% for females for saturated fat intake and 9.8% and 6.4% respectively for any history of polyps.

Gonadal dysfunction in patients receiving chemotherapy for cancer.

Abstract: Since the introduction of antineoplastic chemotherapy, lasting clinical remissions have been obtained for many patients with acute lymphoblastic leukemia, Hodgkin's disease, gestational trophoblastic tumors, and other malignancies. With this therapeutic success there have been concerns about persistent or delayed toxicities of cancer chemotherapy that may become clinically significant for long-term survivors. Gonadal toxicity and infertility occur in many men, women, and children treated with antineoplastic drugs. In this paper we review the clinical syndromes of chemotherapy-related gonadal toxicity and discuss how particular drug classes, doses, or combinations correlate with the degree of gonadal injury and with the potential for recovery of function. Further, we examine how drug effects on germ cell production and endocrine function vary with the age of the patient at the time of treatment. Finally, we comment on the need for long-term prospective studies of fertility, teratogenesis, and mutagenesis in patients receiving cancer chemotherapy.

Radioimmunodetection of cancer with radioactive antibodies to carcinoembryonic antigen

Abstract: Our recent clinical experience in the radioimmunodetection of cancer in 142 patients with a proven history of cancer is summarized. 131 I-labeled affinity-purified goat immunoglobulin G having 70% immunoreactivity with carcinoembryonic antigen (CEA), representing a radiation dose ranging from 0.7 to 2.1 mCi/70 kg patient (2 to 3 µg/kg immunoglobulin G protein), was administered i.v. Anterior, posterior, and lateral radioscans of the chest and abdomen were made routinely at 24 and 48 hr with a γ-scintillation camera. Computer-assisted processing of the images in order to subtract 99m Tc background radioactivity was used to enhance the tumor-related activity, this method resulting in an average 2.5-fold enhancement of the tumor images. A very high percentage of tumor detection was achieved in most of the epithelial cancers studied. The overall sensitivity (true-positive rate) in the four major cancer types studied was as follows: colorectal cancer, 85%; ovarian cancer, 88%; cervical cancer, 90%; and lung cancer, 71%. The specificity (true-negative rate) of the method was likewise very high, ranging from 83 to 100%. In some cases, tumor radioimmunodetection was positive when other detection methods failed. The smallest tumors detectable by this method of radioimmunodetection appeared to be about 2 cm. Metastatic tumors could be localized in a number of patients with normal plasma CEA titers, although in colorectal, cervical, and lung cancer patients there appeared to be a correlation between positive radioimmunodetection and plasma CEA elevation. In general, however, radioimmunodetection was more reliable in detecting cancer among the patient population studied than were the plasma CEA assay results. High amounts of circulating CEA did not appear to prevent successful cancer radioimmunodetection. No untoward or hypersensitivity reactions were found among the patients studied, even when radioimmunodetection was repeated. Evaluation of the clinical findings in the 142 cancer patients studied revealed 116 nonneoplastic benign disease conditions, of which only 2 showed some evidence of radioantibody localization (less than 2%). Administration of radiolabeled normal goat immunoglobulin G to 22 cancer patients, some of whom were already shown to be positive for radioimmunodetection with radioactive CEA antibody, resulted in only 4 of 32 tumor sites with some evidence of transient radiolocalization; 3 of these 4 sites were massive lesions at least 10 cm in diameter.

Spontaneous cancer and its possible relationship to oxygen metabolism.

Abstract: Mortality statistics for cancer in various countries and periods of time indicate that there has been little effect of industrialization on the inherent or spontaneous rate of occurrence of cancer. From U.S. cancer statistics and the BEIR values [Report of the Advisory Committee on the Biological Effects of Ionizing Radiation (1979)] for radiation dose response, the ionizing radiation exposure required to produce a number of cancers equal to this spontaneous incidence was estimated to lie between 450 and 2100 rads (1 rad = 0.01 J/kg). From these "cancer equivalent" doses the number of single-strand DNA breaks required to produce the spontaneous cancers is estimated to be 0.26-1.3 per cell DNA per day. It is suggested that the univalent reduction of oxygen in normal metabolism to O2- and subsequent production of more harmful radicals is the source of the DNA defects that, in cases where the defense mechanisms fail, lead to spontaneous cancer in the individual.

Prognostic implications of fibrotic focus (scar) in small peripheral lung cancers.

Abstract: Peripheral lung cancers frequently possess a fibrotic focus or scar in their center or beneath the pleura. We reexamined 58 cases of peripheral lung cancer of less than 3 cm in diameter (48 adenocarcinomas, two large cell carcinomas and eight squamous cell carcinomas) which were removed surgically between June 1962 and July 1973. Analyses of the cases revealed that in adenocarcinoma with increased collagenization or hyalinization in the fibrotic focus, the degree of pleural invasion and incidence of lymph node metastasis and blood vessel invasion were greater and thus the prognosis of the patient was poorer than in cases with no or slight collagenization. The results also indicate that the characteristics of the central fibrotic focus are probably more important than the size of the tumor for estimating the prognosis of patients with peripheral adenocarcinoma of less than 3 cm in diameter. The same might be said of peripheral large-cell carcinoma. However, the prognostic importance of the fibrotic focus was not confirmed in cases of peripheral squamous-cell carcinoma. Although the central or subpleural scar has long been the basis of the scar cancer concept, alternate explanations were considered, namely, that scar formation occurred along with tumor development, rather than before, in the case of adenocarcinomas.

Nutrition and its relationship to cancer

Abstract: Publisher Summary Nutrition is related to the development of cancer in three ways: (1) food additives or contaminants may act as carcinogens, cocarcinogens, or both; (2) nutrient deficiencies may lead to biochemical alterations that promote neoplastic processes; and (3) changes in the intake of selected macronutrients may produce metabolic and biochemical abnormalities, either directly or indirectly, which increase the risk for cancer. Specific carcinogens play a minor role as initiators in the relationship between nutrition and the development of cancer. This chapter covers six types of cancer: large bowel cancer, colon carcinogenesis, stomach cancer, cancer of the upper alimentary and respiratory tract, cancer of the pancreas, and breast cancer. In four of these—breast, large bowel, stomach, and head and neck—the epidemiologic evidence is overwhelming that nutritional factors have a major etiological role. Dietary factors are also implicated in the etiologies of the two remaining types of cancer—pancreas and prostate—but the epidemiologic evidence is not overwhelming. The chapter also presents an evaluation of the status of the relationship between nutrition and cancer in man, discusses the use of animal models to determine if the etiological factors established for man can be modified in an experimental setting, and makes recommendations for additional research and possible preventive measures.

A Case-Control Study of Menopausal Estrogen Therapy and Breast Cancer

Abstract: The association between estrogen replacement therapy and female breast cancer was studied in two Los Angeles area retirement communities. The 138 study cases of breast cancer occurring in residents younger than 75 years were compared with age- and race-matched community control subjects. The risk ratio for a total cumulative dose in excess of 1,500 mg was estimated to be 2.5 in women with intact ovaries. This increase was present using various independent sources of drug usage information but was inconsistent at low dose and undetectable in oophorectomized women. No important sources of confounding could be identified, and no risk modifiers could be identified except for a history of surgically confirmed benign breast disease. In such women with intact ovaries, the risk ratio for a high cumulative dose rose to 5.7 relative to nonusers with normal breasts. ( JAMA 243:1635-1639, 1980)

Oral contraceptives and breast cancer

Abstract: A study on the possible effect of (OCs) oral contraceptives on breast cancer risk was conducted at the Group Health Cooperative of Puget Sound in Seattle Washington. Exposure and menopausal data were available on women and controls. Among the women aged 31-5 20% used OCs during the period ending June 30 1976 as compared with 13% 2 years later. For those women aged 51-5 user prevalence declined from 2% to 0.3%. 76 of 132 women with breast cancer were premenopausal and 4 were under 30 years of age. Estimates of breast cancer rates in the group of current OC users and nonusers were not adjusted for potential confounding by other risk factors; these were later assessed into a multiple logistic function. Those factors were: age ponderal index age at menarche age at 1st pregnancy history of benign breast disease education and race. Current OC use was entered into the risk function in the form of age-use interaction terms. 1 aspect of the case-control comparison which did not correspond to the population-based findings was the apparent protective effect of current OC use in the group ages 31-40. Among those currently using OCs there is a preponderance of long-term users; no such trend exists among past users. Data from this study indicate that there may be a relation between OC use and breast cancer which is age dependent. Within the age group 31-45 years the incidence in current users (0.71/1000 women-years) was nearly identical to nonusers (0.65/1000 women-years) however current OC use was associated with a strong increase in breast cancer risk in premenopausal women 46-55 years. Other factors for which the breast cancer risk ratio may increase with age include pregnancy and endocrine risk factor. Relationships previously noted which are included in these data include associations between risk and nulliparity educational level and slimness (for women who are premenopausal).

Breast thermography and cancer risk prediction

Abstract: Thermography makes a significant contribution to the evaluation of patients suspected of having breast cancer. The obviously abnormal thermogram carries with it a high risk of cancer. This report summarizes the results of patients with questionable or stage Th III thermograms. From approximately 58,000 patients, most of whom had breast complaints, examined between August 1965 and June 1977, the conditions or a group of 1,245 women were diagnosed at initial examination as either normal or benign disease by conventional means, including physical examination, mammography, ultrasonography, and fine needle aspiration or biopsy, when indicated, but nevertheless categorized as stage Th III indicating a questionable thermal anomaly. Within five years, more than a third of the group had histologically confirmed cancers. The more rapidly growing lesions with shorter doubling times usually show progressive thermographic abnormalities consistent with the increased metabolic heat production associated with such cancers. Thermography is useful not only as a predictor of risk factor for cancer but also to assess the more rapidly growing neoplasms.

Risk of Breast Cancer in Women With Benign Breast Disease

Abstract: A group of 1,489 white women were treated in a private surgery practice from 1940 through 1975 for biopsy-proved benign breast disease, and 1,441 were followed through 1976 for the development of breast cancer. Average duration of follow-up was 12.9 years for a total of 18,617 person-years of observation. Information was collected from a set of questions devised in 1941 and asked of all subjects at the time of their initial office visit, follow-up interview conducted in 1976, and a standardized histology review of the slides from the initial benign lesions and the subsequent cancers. The current pathology review indicated that 66 of the women developed breast cancer. The incidence rate was 3.55 per 1,000 person-years, which is 2.10 times that of the general population. When multiple disease types and other variables were controlled for, excess risk of breast cancer was related to the presence of fibrocystic disease. In women with fibrocystic disease, excess risk was particularly related to the presence of epithelial hyperplasia and/or papias not related to the presence of fibroadenoma alone, but it was related to the presence of fibroadenoma in women with concomitant fibrocystic disease. The excess risk was also directly related to the estimated size of the initial benign mass and was greater for women with bilateral than with unilateral benign lesions.