Showing papers on "Breast cancer published in 1980"
TL;DR: The prognostic effect of weight loss prior to chemotherapy was analyzed using data from 3,047 patients enrolled in 12 chemotherapy protocols of the Eastern Cooperative Oncology Group and increased with increasing number of anatomic sites involved with metastases, but within categories of Anatomic involvement, weight loss was associated with decreased median survival.
2,178 citations
TL;DR: Preliminary analysis suggests that the presence of PgR may be a better marker of tumor hormone dependence than quantitative ER, which is an important independent prognostic indicator of higher rate of recurrence and shorter survival.
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.
740 citations
TL;DR: In blacks, breast cancer was diagnosed in a relatively more advanced stage than in whites, and survival and cure rates were generally lower for blacks, and such lower rates seem to be associated with the relatively advanced stage of the disease.
Abstract: This is a resume of a Breast Cancer Survey carried out by the American College of Surgeons in 1978. Four hundred and ninety-eight hospitals in 47 states, Washington, D. C., and Puerto Rico participated, contributing a total of 24,136 female patients with histologically confirmed breast cancer. In these patients, five-year cure rates were 60.5% for clinically localized disease and 33.9% for regional disease. Five-year survival rates were 72.8% for localized disease and 49.1% for regional disease. From the 1960's into the early 1970's, there was a gradual shift away from radical mastectomy towards so-called modified radical mastectomy. In a group of patients treated by either radical or modified mastectomies, the axillary nodal status, size of the tumor, and location of the tumor were examined in relation to the prognosis. In the study of number of metastatic nodes in the axilla, there were reduced cure and survival rates in patients with one or more positive nodes as compared to those with negative axillary nodes. With the increase in the number of positive nodes, there was a continuing associated decline in survival and cure. The clinical size of the tumor also correlated well to the prognosis. With the increase in the size of the tumor, there was a gradual increase in the probability of axillary nodal involvement. However, in the group of patients with tumor size smaller than 1 cm, axillary metastasis occurred in 25%. When the axillary nodes were involved, the cure rate in those patients was not significantly better than the rates for those with larger primary tumors in this study. Tumors located in the medial half of the breast were associated with a slightly lower cure rate than those in the lateral half. Young women under 35 years of age had poorer survival and cure rates, although in women 35–44 years of age, the five-year results were comparable to the older group of patients. In blacks, breast cancer was diagnosed in a relatively more advanced stage than in whites. Survival and cure rates were generally lower for blacks, and such lower rates seem to be associated with the relatively advanced stage of the disease.
633 citations
TL;DR: It is concluded that leukocyte interferon can induce tumor regression in patients with advanced cancer and will remain on study for 52 to 63 weeks.
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.
521 citations
TL;DR: The 46K protein, which accounts for 40% of 35S-methionine incorporation into secreted proteins, is only induced by steroids able to interact with the estrogen receptor, and makes these cell lines excellent in vitro systems for studying the mechanism of estrogen and anti-estrogen action.
492 citations
TL;DR: High PG production occurred early in the natural course of breast cancer and was elevated in tumors at a time when active tumor invasion proceeded, indicated that elevated PG production can be used as a marker of high metastatic potential for neoplastic cells in breast cancer.
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.
371 citations
Journal Article•
TL;DR: It has been demonstrated by us that tumor heterogeneity is not merely an interesting biological observation but that it possesses therapeutic significance as well and the results indicate that metastatic cellular heterogeneity is an important factor to be considered when assessing therapeutic response.
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.
360 citations
336 citations
TL;DR: Improvements in mammography in the past 25 years have made it possible to detect before surgery many lesions with a high probability of being pre‐invasive carcinoma, and these cancers are virtually all cured by mastectomy.
Abstract: Improvements in mammography in the past 25 years have made it possible to detect before surgery many lesions with a high probability of being pre-invasive carcinoma. Because these cancers are virtually all cured by mastectomy, there has been considerable interest in alternative types of treatment. Retrospective studies of pre-invasive carcinoma treated by biopsy only revealed subsequent carcinoma in 30 to 40% of patients. Among women with lobular carcinoma in situ (LCIS), the frequency of subsequent carcinoma was nine times the expected rate, and mortality due to the disease was 11 times greater than expected. The risk of later invasive carcinoma appeared to involve both breasts equally when LCIS was present and to be largely limited to the breast that harbored intraductal carcinoma (IDC). When mastectomy was performed for pre-invasive carcinoma, unsuspected invasion was found in 4% of patients with LCIS and 6% with IDC.
It remains to be determined whether multicentric preinvasive carcinoma will follow the same course in patients with palpable invasive carcinoma treated by partial mastectomy and some form of adjuvant therapy. At present, it is prudent to treat pre-invasive breast cancer by ipsilateral mastectomy with low axillary dissection and to perform a contralateral breast biopsy. However, prospective, controlled investigations are urgently needed to identify groups of patients with a high or low risk of developing invasive carcinoma and to determine whether non-surgical treatment can alter the course of pre-invasive disease. By pursuing these studies, it may ultimately be possible to measure the success of breast cancer detection by the number of patients cured without mastectomy.
330 citations
TL;DR: A biologically based two-stage model for carcinogenesis is presented that relates events occurring at the cellular level to epidemiologic features of breast cancer in females and it is argued that hormones are likely to be unimportant in determining overall risk in populations.
Abstract: A biologically based two-stage model for carcinogenesis is presented that relates events occurring at the cellular level to epidemiologic features of breast cancer in females. This model, which accommodates the physiologic responses of breast tissue to menarche, menopause, and pregnancy, predicts age-specific incidence curves that are in close quantitative agreement with those observed in six test populations: Connecticut, Denmark, Finland, Slovenia, Iceland, and Osaka, Japan. According to the model, hormones influence the epidemiology of breast cancer in females by their action on the kinetics of growth of nonneoplastic breast tissue. As a consequence, it is argued that hormones are likely to be unimportant in determining overall risk in populations. The protective effect of an early first birth predicted by the model is in good quantitative agreement with data from a multinational study. Other epidemiologic features of breast cancer are logically explained within the framework of the model. No feature of the epidemiology of breast cancer requires that premenopausal and postmenopausal breast cancer be considered distinct entities from the point of view of pathogenesis.
293 citations
TL;DR: Whether the breast cancer reaches diagnosis before or after menopause, the bulk of evidence examined here supports the view that it has a common cause and is subject to modifying influences over the long period of cancer latency.
Abstract: In a case-control study of 1868 breast cancer patients and 3391 control patients we searched for characteristics that predicted risk of breast cancer diagnosed before and after menopause. Common to increased risk of this disease in both periods of womanhood were: early menarche and late menopause; delayed marriage and first childbirth; more nulliparity or reduced gravidity and parity; reduced frequency of abortions; shorter overall child-bearing interval; more advanced education, higher socioeconomic status, and more contraceptive usage; and familial tendencies toward the disease. Breast cancer patients diagnosed before menopause were leaner than controls at age 20 and at time of diagnosis, but breast cancer risk in the postmenopausal period was related to increased weight-for-height at diagnosis and greater weight-for-height at diagnosis and greater weight gain since age 20. Postmenopausal breast cancer patients had a longer interval between first and second childbirths. Frequency and duration of the gravid state, inversely related to breast cancer risk, were largely dependent on contraceptive practices rather than unexplained infertility per se. Whether the breast cancer reaches diagnosis before or after menopause, the bulk of evidence examined here supports the view that it has a common cause and is subject to modifying influences over the long period of cancer latency.
TL;DR: The biologic behavior of ISLC and ISDC may be different with regard to their propensity to invade and their overall prognosis, and the infiltrative form of lobular and ductal carcinoma, were found to have the same prognosis.
Abstract: This study evaluates the data of noninvasive (in situ) lobular (ISLC) and ductal (ISDC) carcinoma, collected from 498 hospitals in a National Breast Cancer Survey, carried out by the American College of Surgeons in 1978. ISLC and ISDC were identified in 323 (3.2%) of 10,054 female patients with lobular and ductal carcinoma, of the total of 23,972 patients with histologically proven breast cancer surveyed (1.4%). The frequency of ISLC was significantly higher (18.5%) than ISDC (2.1%) suggesting a less agressive nature of ISLC, with a slower progression to invasion than ISDC. There was a different age distribution of ISLC and ISDC: about 80% of ISLC and 50% of ISDC were diagnosed in patients who were less than 54 years old, and the incidence showed a marked decrease in the older age groups in ISLC, whereas the incidence remained high in the following decade in ISDC. In this series there was a distinctly better five-year cure rate in the patients with ISLC (83.5%) than in the patients with ISDC (68.8%), in spite of the fact that radical surgery was performed more frequently in ISDC (67.8%) than ISLC (36.3%). The recurrence rate was five times higher (10.5%) in ISDC than in ISLC (2.5%). In black patients the recurrence rate (21.3%) was significantly higher in ISDC than in white patients (9.3%). In the present study there were no statistically significant differences in the five-year cure and recurrence rate in patients with noninvasive carcinoma, treated by more conservative procedures (72.9% and 8.5%) and those treated by more extensive surgeries (76.2% and 7.7%). The results of this study suggests that the biologic behavior of ISLC and ISDC may be different with regard to their propensity to invade and their overall prognosis. In contrast, the infiltrative form of lobular and ductal carcinoma, were found to have the same prognosis, regardless of the type of operative procedure performed.
TL;DR: This chapter 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.
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.
TL;DR: The association between estrogen replacement therapy and female breast cancer was studied in two Los Angeles area retirement communities and no risk modifiers could be identified except for a history of surgically confirmed benign breast disease.
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)
TL;DR: There has arisen an altered concept of cancer biology during the past two decades and the National Surgical Adjuvant Project for Breast and Bowel Cancers has made a major contribution to the change through findings from a series of prospective randomized clinical trials.
Abstract: Disagreement about local-regional management of primary breast cancer is related to differences in perception of the biology of the disease. Other factors are secondary and obscure the reality that all treatment must be related to biological considerations; otherwise, the basis for therapy is relegated to speculation and to personal experience. As a result of extensive laboratory and clinical studies during the past two decades, there has arisen an altered concept of cancer biology. The National Surgical Adjuvant Project for Breast and Bowel Cancers (NSABP) has made a major contribution to the change through findings from a series of prospective randomized clinical trials. That group of American and Canadian investigators has implemented a series of trials aimed at answering biological as well as clinical questions. Those studies have not only been concerned with defining proper local-regional treatment but have also pointed out the need for, and value of, systemic therapy when used in conjunction with operation.
This report will provide an overview of past and present NSABP contributions and will consider those findings in relation to observations from other clinical trials of pertinence. It will emphasize that controversies concerning breast cancer management are related to biological issues that cannot be resolved by “populism” or appeals to emotion.
TL;DR: Data from this study indicate that there may be a relation between OC use and breast cancer which is age dependent, and current OC use was associated with a strong increase in breast cancer risk in premenopausal women 46-55 years.
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).
TL;DR: The major findings indicated that physical disability did not necessarily relate to an increase in emotional disturbance, and adjuvant radiation therapy was a potent source of distress during primary cancer treatment, and at least one-third of all patients in each category reported needing help with household chores.
Abstract: The authors studied 146 breast cancer patients representing three different treatment regimens by means of a structured interview, open-ended questions, and a modified Psychiatric Status Schedule. The major findings indicated that physical disability did not necessarily relate to an increase in emotional disturbance. The most emotionally disturbing time was the first recurrence of the breast cancer, and the most common disturbance reported in all three treatment groups was in the area of mate role functioning. In addition, adjuvant radiation therapy was a potent source of distress during primary cancer treatment, and at least one-third of all patients in each category reported needing help with household chores.
TL;DR: Thermography makes a significant contribution to the evaluation of patients suspected of having breast cancer and is useful not only as a predictor of risk factor for cancer but also to assess the more rapidly growing neoplasms.
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.
TL;DR: Under estrogen-deficient conditions, condsitions approximating postmenopausal status in women, a dormant state was established between MCF-7ED cells and murine mammary stroma which could be maintained several months, and should be useful for defining host and cancer cell determinants in estrogen-responsive breast cancer growth.
TL;DR: A group of 1,489 white women 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, indicating that 66 of the women developed breast cancer.
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.
TL;DR: Three VACURG studies report that patients with low stage disease who are treated with estrogen have a higher death rate than men not receiving estrogen and in patients with high stage disease, delayed hormonal therapy is as effective as early hormonal therapy.
Abstract: The principle goal of hormonal therapy in the treatment of prostatic cancer, as Huggins suggested in 1941, is the suppression of androgenic stimuli. Consequently, the treatment of advanced prostatic cancer has consisted of orchiectomy, estrogen administration, antiandrogen therapy, adrenalectomy or hypophysectomy, or a combination of some of these. Although the three VACURG studies are subject to several valid criticisms, they provide the best available information to date. In summary, these studies report 1) patients with low stage disease who are treated with estrogen (diethylstilbestrol 5 mg/day) have a higher death rate, mainly cardiovascular, than men not receiving estrogen and 2) in patients with high stage disease, delayed hormonal therapy is as effective as early hormonal therapy. Castration appears to be as effective as treatment with estrogens or a combination of the two and does not evoke the untoward side-effects of estrogen administration. Although subjective improvement has been observed following adrenal or pituitary ablation, the duration of response is usually short, and consequently these procedures are used infrequently now. Experience with the use of antiandrogens is even more limited. Efforts must continue to develop means of predicting hormonal responsiveness. If receptor measurements prove to be an accurate means for predicting the hormonal responsiveness of prostatic cancer, as they have in breast cancer, then our current plan of treatment will need modification. In those men who are unlikely to respond to hormonal therapy, early chemotherapy should be instituted.
TL;DR: Three populations of women exposed to ionizing radiation: survivors of the Hiroshima and Nagasaki atomic bombs, patients in Massachusetts tuberculosis sanitoria who were exposed to multiple chest fluoroscopies, and patients treated by X-rays for acute postpartum mastitis were analyzed.
Abstract: Breast cancer incidence data were analyzed from three populations of women exposed to ionizing radiation: survivors of the Hiroshima and Nagasaki atomic bombs, patients in Massachusetts tuberculosis sanitoria who were exposed to multiple chest fluoroscopies, and patients treated by X-rays for acute postpartum mastitis in Rochester, New York. Parallel analyses by radiation dose, age at exposure, and time after exposure suggested that risk of radiation-induced cancer increased approximately linearly with increasing dose and was heavily dependent on age at exposure; however, the risk was otherwise remarkably similar among the three populations, at least for ages 10 to 40 years at exposure, and followed the same temporal pattern of occurrence as did breast cancer incidence in nonexposed women of similar ages.
TL;DR: All options should be considered for developing research and teaching in thermopathology, starting from the basic knowledge of thermophysics and thermophysiology, certainly the only way of improving the acceptance of thermography by physicians and consequently by the health care authorities.
Abstract: Various methods are now available for clinical exploration of the breast. The most commonly used methods provide information essentially on morphology and structure, including macroscopic data (palpation, radiography, echography) and microscopic data (cytology, histology). By contrast, the thermal methods, among them skin thermography using infrared scanners or liquid crystals films, offer the advantage of giving information on thermophysiology. The superficial thermal pattern of the breast is in fact related to metabolism and vascularization within the underlying tissues. It may therefore be changed significantly as a result of normal phenomena (e.g., the menstrual cycle or pregnancy) or pathological processes. Because cancers vary so widely, not only in their histologic features but also in their physiological properties (e.g., the doubling time of tumors ranges from approximately 50 to 700 days), it would be regrettable to ignore the thermological dimension, which is related to the temporal properties of cancer. In spite of continuous progress in thermographic techniques as well as in standardization of examining conditions and image analysis, however, many physicians still hesitate to consider thermography as a useful tool in clinical practice. This attitude is somewhat amazing for those who have a long experience in thermography. It may be explained considering that physical and biological bases are not familiar to the physicians. All other methods of investigation refer to topics of medical teaching, e.g., radiography and echography to anatomy, or scintigraphy and biochemical assays to metabolic physiology. On the contrary, thermodynamics and thermokinetics are, for most physicians, strange sciences, though man is more or less unconsciously experiencing heat production and heat exchanges in every situation that he is undergoing. In the present state of the art, all options should be considered for developing research and teaching in thermopathology, starting from the basic knowledge of thermophysics and thermophysiology. This is certainly the only way of improving the acceptance of thermography by physicians and consequently by the health care authorities. Since we started with thermography 14 years ago, clinical and fundamental research have been simultaneously developed in our Laboratory of Biomedical
TL;DR: Multivariate analyses disclosed that both age and tumor differentiation are associated with the ER status, and considered a possible explanation for the dichotomy of response to adjuvant chemotherapy observed in pre and postmenopausal women.
Abstract: Estrogen receptor (ER) status was correlated with a large number of pathological and clinical characteristics of 178 invasive breast cancers. Positive ER was found to be significantly associated with high nuclear and low histologic grades, absence of tumor necrosis, presence of marked tumor elastosis, and older patients. These pathologic parameters enumerated are either directly or indirectly related to tumor differentiation suggesting that ER represents another index of this latter. Multivariate analyses disclosed that both age and tumor differentiation are associated with the ER status. Well-differentiated tumors were more frequently ER+ in older women. Inclusion of an estimate of tumor necrosis as well as patient age appears to allow for further discrimination of ER status in poorly differentiated lesions. Considerations relative to ER and tumor differentiation provide a possible explanation for the dichotomy of response to adjuvant chemotherapy observed in pre and postmenopausal women.
TL;DR: This technique of radical radiotherapy in early breast cancer is recommended because of this high rate of tumor control, associated with a low rate of normal tissue damage and survival figures comparable to those achieved by radical surgery.
Abstract: The 5 year results of radical radiation therapy in operable, infiltrating breast cancer (T1, T2, T3; NO, N1a, N1b) in 177 patients are presented. The treatment protocol included a pre-radiotherapy tumorectomy for T1 and certain T2 tumors (those less than 3cm diameter). Patients with larger tumors were treated by radiotherapy alone. The treatment technique incorporated both conventional fractionated radiotherapy (60 Co and electrons) and endocurietherapy (192 Ir). At 5 years, the uncorrected, disease-free survival rates were 84 % for T1, 79% for T2 and 56% for T3: loco-regional persistent or recurrent disease was seen in 4.5 % of patients with Tl disease, 7.5 % of those with T2, and 23 % of T3 patients; 16 mastectomies had been performed. Of the patients with T1 and T2 disease, 95 % had retained their breast and the esthetic result was judged to be good in 75 %. We recommend this technique of radical radiotherapy in early breast cancer because of this high rate of tumor control, associated with a low rate of normal tissue damage and survival figures comparable to those achieved by radical surgery.
TL;DR: Findings suggested that any therapeutic procedure for either invasive or non‐invasive ductal carcinoma that does not include total mastectomy may leave behind foci of cancer, which are a threat to the patient.
Abstract: One hundred eighty-nine biopsies have been performed for clinically occult mammary lesions, detectable by mammography but not clinically apparent. Fifty-two cancers were demonstrated within this group, including 26 invasive ductal cancers, seven micro-invasive ductal cancers, 14 non-invasive ductal cancers, and five lobular carcinomas in situ. All mastectomy specimens were examined for multicentric foci of breast cancer in quadrants other than that in which the primary lesion was located. Of the invasive ductal cancers, 40% were multicentric. Of the micro-invasive ductal cancers, 57.1% were multi-centric. Of the non-invasive ductal cancers, 45.5% were multicentric. The one mastectomy specimen from a patient with lobular carcinoma in situ did not have evidence of residual disease. The overall incidence of multicentricity in the 43 specimens examined was 44.2%. These findings suggested that any therapeutic procedure for either invasive or non-invasive ductal carcinoma that does not include total mastectomy may leave behind foci of cancer, which are a threat to the patient.
TL;DR: Data from the 1969-71 Third National Cancer Survey were used to study the association of cancer incidence with income and education as indicated by census tract of residence, and income had a stronger association than did education with cervical cancer incidence.
Abstract: Data from the 1969-71 Third National Cancer Survey were used to study the association of cancer incidence with income and education as indicated by census tract of residence. Also considered was the effect of adjustment for differences in socioeconomic distribution on the observed excess risk of cervial cancer and lower risk of breast cancer among black women compared to white women. Strong positive associations with both income and education were found, with the rates based on 19,344 breast cancer cases among white women. These observations were noted in most geographic areas studied. The relative risk showed little apparent relationship to age. The rates based on 1,570 cases among black women indicated a strong positive association with education but not with income. Socioeconomic adjustment reduced by almost one-half the black-white difference in breast cancer rates, and education had a stronger effect than did income. White women continued to have a significantly higher rate after such adjustment. Conversely, the incidence of cancer of the cervix showed strong negative associations with each of the two variables among both the 3,802 cases in white women and 954 cases in black women. The negative gradient decreased with age and was apparent in almost all the areas. The excess risk among black women was reduced by two-thirds with socioeconomic adjustment, though the rates remained significantly different. Income had a stronger association than did education with cervical cancer incidence.
TL;DR: The relation between replacement estrogens and breast cancer in menopausal women (age 45-64 years) was evaluated in the Group Health Cooperative of Puget Sound, Washington State, a prepaid health care organization with fully computerized information on outpatient drug use and hospital diagnoses.
Abstract: Data from a Group Health Cooperative a consumer-owned cooperative in Washington state were analyzed to assess any relationship between the use of replacement estrogens and the incidence of breast cancer in a group of menopausal women (aged 45-64 years). This group plan has fully computerized outpatient drug use and hospital diagnoses information. Menopausal women were categorized as natural or hysterectomized. Among naturally menopausal women there were 60 cases of breast cancer; of these 18 were current estrogen users (30%). In these women there was a positive association between current estrogen use and breast cancer (RR=3.4; 90% confidence interval 2.1-5.6). This relative risk (RR) estimate of 3.4 between estrogen users and nonusers became stronger when naturally menopausal women in the younger age range (45-54) were examined separately. The association of the 45-54 year-old group rose to a relative risk of 10.2 whereas among the older naturally menopausal women the relative risk dropped to 1.9. There appeared to be little association between current estrogen use and breast cancer when menopause was categorized as hysterectomized. In this group the relative risk was 1.1 with a 90% confidence interval of .7-1.8.
TL;DR: The chapter highlights the information that estrogen receptor (ER) provides in the primary tumor and presents some innovative uses of combined endocrine chemotherapy.
Abstract: Publisher Summary This chapter discusses the endocrine therapy and the use of steroid receptors in human breast cancer. The chapter highlights the information that estrogen receptor (ER) provides in the primary tumor. ER assays select a subset of patients who recur early and have poor survival. They help to select the agents to be used in adjuvant therapy since only about one-half of breast cancer patients are cured by surgical and/or radiation therapy of the primary tumor. The majority of these patients have tumors confined to the breast without extension to the axillary lymph nodes. ER assays in the primary tumor predict for responsiveness to endocrine therapy if and when a patient develops metastatic disease. The presence or absence of ER in a biopsy of metastatic breast cancer correlates well with the response of cancer to endocrine therapy. The response rate to endocrine therapy directly correlates with the absolute amount of ER found at biopsy. The chapter also presents some innovative uses of combined endocrine chemotherapy.