Showing papers in "Breast Cancer Research and Treatment in 1986"

Autocrine and paracrine growth regulation of human breast cancer

Abstract: We consider the hypothesis that estrogen control of hormone dependent breast cancer is mediated by autocrine and paracrine growth factors secreted by the breast cancer cells themselves. Though we show direct, unmediated effects of estrogen on specific cell functions, we also provide evidence that human breast cancer cells secrete a collection of growth factors (IGF-I, TGFα, TGFβ, a PDGF-like competency factor, and at least one new epithelial colony stimulating factor). Some of these are estrogen-regulated in hormone dependent cells, and are constitutively increased in cells which acquire independence either spontaneously or byras transfection. Collectively, the secreted growth factors are capable of promoting tumor formation by MCF-7 cells in nude mice, though not to the same extent as estrogens. There would seem to be potential for clinical intervention in the autocrine and paracrine control of breast cancer cells, including some cells which are no longer dependent on estrogens.

Cell kinetics of histologic variants of in situ breast carcinoma.

Abstract: A thymidine labeling study of cell kinetics of 61in situ breast carcinomas showed relationships between histological characteristics and kinetics. The thymidine labeling index (TLI) was significantly lower in cribriform-papillary intraductal carcinoma (median 1.30%, geometric mean 1.18%, mean 1.83 ± 0.45%) and lobular carcinomain situ (median 1.43%, geometric mean 1.12%, mean 1.63 ± 0.46%) than in comedo intraductal carcinoma (median 4.40%, geometric mean 3.74%, mean 5.15 ± 0.86%). The results for solid intraductal carcinoma, which is a less well defined and more heterogeneous entity, were intermediate (median 2.45%, geometric mean 2.40%, mean 3.32 ± 0.80%). When invasive carcinoma was also available for kinetic study, the TLI ofin situ and invasive components were usually similar (r = 0.66). The data indicate that the TLI usually does not change during the transition fromin situ to invasive carcinoma. Cribriform-papillary intraductal carcinoma is a slowly proliferating entity that gives rise to slowly proliferating invasive carcinomas with relatively high levels of estrogen and progesterone receptors. Lobular carcinomain situ similarly has low proliferative rates and gives rise to slowly proliferating invasive carcinomas. Intraductal comedocarcinoma has relatively high proliferative rates and gives rise to invasive carcinomas with high proliferative rates that often are receptor-negative. Nine of the 11in situ carcinomas that were associated with invasive tumor and subsequent local recurrence or metastasis had TLIs above the median, and seven were comedo type with high TLIs. Our observations from thymidine labeling are consistent with a viewpoint regarding cribriform-papillary intraductal carcinoma as relatively bland, and comedo intraductal carcinoma as a distinctly more dangerous entity. Solid intraductal carcinoma seems to resemble cribriform-papillary more closely than comedo intraductal carcinoma.

Physiologic, biochemical, and cytologic aspects of nipple aspirate fluid.

Abstract: In 1923, Geoffry Keynes wrote, 'the breast is a gland which throughout life is exhibiting some secretory activity, the difference between a lactating and a nonlactating breast being one partly of degree and partly of the chemical constitution of the secretion' (1). He emphasized that the physiology of the breast entails not merely a secretory, but by physiologic necessity, a continuous absorptive activity. Except during lactation, the mouths of the nipple ducts are normally not open but tightly occluded by keratin plugs, and secretion can rarely escape. Since the 1920s, pathologists have intensively studied the histopathology of the female breast in health and disease. The description of the progression from normal epithelium through hyperplasia, atypical hyperplasia, carcinoma in situ to cancer is now well understood and detailed in several publications (2-6). Epithelial atypical hyperplasia has been identified as a specific high-risk precursor lesion in breast cancer. The intraluminal cells and secretions in the alveolar-ductal system, although evident in histologic sections of breast tissue, have received little attention. Most pathologists considered these cells and secretions to be sloughed-off degenerating epithelium and proteinaceous material, and of little biological interest. Exceptions to this view were the studies of Keynes and of Bonser, Dossett, and Jull (7), and the more recent studies by several investigators (8-17) who have used nipple aspirate fluid for cytologic diagnosis and biochemical research. Recent studies of nipple aspirate secretions have emphasized the biochemical nature of the secretion, nipple aspirate cytology and its potential relationship to the morphology (atypical hyperplasia) and function of the alveolar-ductal system of the breast, and the epidemiology of benign breast disease and breast cancer.

Prognostic implication of labeling index versus estrogen receptors and tumor size in node-negative breast cancer.

Abstract: The paper analyzes the relation among tumor size (T), estrogen receptor (ER) status, and labeling index (LI) and their relative merits in predicting the relapse-free (RFS) and overall survival (OS) in 215 node-negative women with primary breast cancer. All patients were subjected to Halsted or modified radical mastectomy; none received postoperative irradiation or systemic adjuvant therapy. The 5-year RFS was 75.3% and OS 89.0%

Paget's disease of the nipple: a ten year review including clinical, pathological, and immunohistochemical findings

Abstract: Thirty-five women with biopsy-proven Paget's disease of the nipple were treated over a 10 year period at the Breast Cancer Unit, Guy's Hospital. Twenty-four (69%) patients had Paget's disease without a palpable mass in the breast; eleven (31%) presented with a palpable mass and Paget's disease of the nipple. Definitive treatment consisted of modified radical mastectomy in 32 patients, radiotherapy only in 2, and one patient had no definitive treatment. All 11 patients with Paget's disease and an associated lump proved to have invasive ductal carcinoma; five also had associated positive axillary nodes. Nine of the 23 patients with nipple changes only, treated by mastectomy, also had invasive carcinoma; three of these had positive axillary nodes. The remaining 14 patients with nipple changes only were found to have in situ ductal carcinoma, which was extensive in the majority of cases. In 13 cases, histological sections of the nipple were examined by immunohistochemical staining which showed that the Paget's cells expressed a keratin phenotype that was specifically characteristic of simple epithelial cells as seen in glandular epithelium. This was quite unrelated to the normal keratin phenotype of the surrounding skin keratinocytes. Clinical, pathological, and immunohistochemical data suggest a mammary origin of the abnormal cells in Paget's disease of the nipple. Mastectomy appears to be the treatment of choice.

Long-term survival following relapse after 5-FU but not CMF adjuvant breast cancer therapy.

Abstract: Beginning in 1974, patients with ≥4 nodes positive following mastectomy were randomized to receive either 5-FU i.v. weekly or CMF i.v. every 2 weeks, both given for 12 months. Median follow-up now exceeds 112 months with nine year results below: Early results based on relapse-free survival favored CMF, but more patients currently are alive on the 5-FU arm. As the survival curves cross at 40 months, the 20% survival advantage for 5-FU did not achieve statistical significance. For 34% of patients failing adjuvant 5-FU, use of combination chemotherapy after relapse (commonly with CMFVP or CMF) resulted in long term survival. In contrast, long-term survival for patients failing adjuvant CMF was unusual. Relapse was detected while under weekly observation in a greater proportion of patients on 5-FU (36%) compared to CMF (6%) adjuvant treatment (p 10 kg associated with a poor prognosis. We conclude that initial improvement in relapse-free survival may not predict long term survival in adjuvant breast cancer trials since both the specific adjuvant therapy given pre-relapse as well as the type of salvage therapy given post-relapse may influence ultimate patient outcome.

Immunological detection and quantitation of alpha transforming growth factors in human breast carcinoma cells.

Abstract: Alpha transforming growth factors (αTGFs) were immunologically detected in the concentrated conditioned medium (CM) prepared from four human breast cancer cell lines and from primary cultures of human mammary epithelial cells, and in the tissue extracts prepared from normal, benign, and malignant breast biopsies. Immunoreactive αTGFs were quantitated by a competitive radioimmunoassay (RIA) using affinity-purified polyclonal sheep anti-rat αTGF antibodies which react with human αTGF but not with human epidermal growth factor (EGF). The relative level of RIA-detectable αTGFs in the CM from the breast cancer cell lines MCF-7, ZR-75-1, T47-D, and MDA-MB-231, and from the CM of primary cultures of human mammary epithelial cells, ranged from 0.02 to 0.85 ng/ml. MCF-7 or ZR-75-1 cells grown in the presence of 17β-estradiol (10−8 M) for 48 h were found to release two- to three-fold more αTGFs into their CM than the same cells grown in the absence of estrogen. In detergent extracts prepared from normal breast tissue, a benign fibrocystic lesion, fibroadenomas and primary breast carcinomas, the relative αTGF concentrations were found to range from 1.5 to 6 ng/mg cell protein. No significant correlations were found between the αTGF levels and the pathological state of the tissues, the estrogen receptor status of the tumors, or the relative amounts of theras gene protein p21ras in the tissues as determined by Western immunoblot analysis. The question of biological relevancy of αTGF for human mammary tumors will require further studies on (a) synthesis and turnover of αTGF, (b) the relationship between immunoreactivity and biological activity of αTGF, and (c) differences in biological responsiveness of mammary tumor cells.

Cytogenetic studies on human breast carcinomas.

Abstract: Cytogenetic studies were performed on cell material obtained from surgical specimens of 50 human breast carcinomas and from 61 cancerous effusions of 46 patients. Classical cytogenetic analyses of numerical chromosome changes and marker chromosomes revealed the non-random involvement of chromosomes #X and #22 as monosomics, of chromosomes #3, #7, and #19 as trisomics, and chromosome #1 (particularly p 13 to q 12) in marker formation. Karyotypic evolution was followed in vitro and in vivo and showed a highly individualistic pattern of stability and variability.

Randomized mammographic screening for breast cancer in Stockholm. Design, first round results and comparisons.

Abstract: In March 1981 a randomized single-view mammographic screening for breast cancer was started in the south of Stockholm. The screened population in the first round numbered 40,318 women, and 20,000 women served as a well-defined control group. The age groups represented were 40–64 years, and 80.7% of the invited women participated in the study. The first round disclosed 128 breast cancers (113 invasive and 15 noninvasive), or 4.0 per 1,000 women. Mean tumour size was 14.1 mm and axillary lymph node metastases were found in 21.8%. Fifty-five per cent of the tumours were small (⩽10 mm) or non-invasive, and 71% were stage I. Participation rates are high in all Swedish trials. The present results differ only slightly from other screening programs; the percentages of patients with axillary metastases and stage II tumours are similar in the Stockholm, Malmo and Kopparberg/Ostergotland studies. Comparisons of cancer prevalence in the various Swedish screening trials show that, in comparable age groups, there are some differences, even when the differences in the natural cancer incidence are taken into account. A decreased mortality was found recently in a Swedish trial in ages above 50 years but not below. In the Stockholm study more than one-third of the participants were aged 40–49 years.

Estrogen sulfates: biological and ultrastructural responses and metabolism in MCF-7 human breast cancer cells.

Abstract: The biological effects and ultrastructural alterations by different estrogen-3-sulfates (E1-3-S and E2-3-S) and estradiol-17-sulfate (E2-17-S) were studied in the MCF-7 mammary cancer cell line in culture. The estrogen-3-sulfates very significantly stimulated the progesterone receptor (PR). The values (in pmoles/mg DNA ± SE) were: control, 0.46 ± 0.09; E1-3-S, 2.24 ± 0.30, and E2-3-S, 2.56 ± 0.45. The value of PR after E2-17-S incubation (0.56 ± 0.24) was similar to the non-treated cells. The PR values obtained by the incubation of unconjugated estrone and estradiol were: 2.63 ± 0.45 and 2.27 ± 0.36, respectively. Analysis of the unconjugated estrogens in the medium indicated significant hydrolysis of estrogen-3-sulfates but not of E2-17-S. Using [3H]-E1-3-S, an important transformation was observed inside the cells, a great part being converted to estradiol (>60% in the nuclear fraction). Electron microscopic examination indicated alterations in the secretory system after incubation with estrogen-3-sulfates similar to those obtained with unconjugated estradiol. The effect provoked by E2-17-S was significantly less than for the other sulfates.

Biological therapy of cancer.

Abstract: Interferons and monoclonal antibodies are among the most promising biological approaches to cancer treatment which have so far been investigated. Both natural and recombinant interferon-alpha preparations have shown activity in a number of trials in hematologic malignancies, even in previously treated patients; activity in solid tumors, however, has been limited. Unconjugated monoclonal antibodies have been safely administered in several small trials and have had therapeutic value on occasion. In spite of a number of remaining problems and questions, monoclonal antibodies and their conjugates seem likely to find a number of distinct roles in cancer treatment; elimination of micrometastases and purging of bone marrow for grafting may be among these roles.

Estrone sulfate: A potential source of estradiol in human breast cancer tissues

Abstract: Local formation of estradiol in human breast tumors could provide a more important source of estrogen than is delivered from plasma. Prior studies have suggested that estrone is primarily synthesized from estrone sulfate. The enzyme 17β-hydroxysteroid dehydrogenase (HSD) would be required to convert estrone to estradiol.

Proliferative index, cytosol estrogen receptor and axillary node status as prognostic predictors in human mammary carcinoma.

Abstract: The predictive value of tumor cell estrogen receptor (ER) content, DNA ploidy, proliferative index (PI) and lymph node involvement was examined in 210 women operated on for primary breast cancer in 1979. At a minimum follow-up of 60 months the highest relapse free survival was observed in patients whose tumours had ER greater than 0.30 fmole/micrograms DNA (ER rich) and PI less than 5% (PI low). Subclassification of tumors in euploid and aneuploid groups gave no prognostic information. When examined by axillary node status (no nodal involvement - involved nodes) both ER and PI contributed prognostic information. Multivariate analysis using Cox proportional hazards model showed that nodal involvement was the strongest predictor of recurrence (p = 0.0007). However, ER and PI contributed significant independent prognostic information (p = 0.048 and p = 0.038), respectively.

Tumor nuclear grade, estrogen receptor, and progesterone receptor: their value alone or in combination as indicators of outcome following adjuvant therapy for breast cancer.

Abstract: Previous reports by us have shown that the outcome of breast cancer patients who have received systemic adjuvant therapy is influenced by tumor estrogen or progesterone receptor (ER or PR) content or by nuclear grade. This publication provides information regarding the relative merit of those three markers. Findings from patients receiving L-PAM plus 5-FU (PF) or PF plus tamoxifen (PFT) indicate that the disease-free survival and survival within each regimen was almost identical when related to either ER, PR, or nuclear grade. Those having tumors with either of the receptors greater than or equal to 10 fmol or a good nuclear grade had a better outcome through five postoperative years than did those with ER or PR 0-9 fmol or poor nuclear grade. The magnitude of the difference was similar for each of the three discriminants. Since they were found to be of equal predictive value, one marker might well serve as a substitute for another. Cox regression analyses, however, clearly indicate that ER, PR, and nuclear grade have an independent influence on outcome and that a more accurate assessment of outcome is obtained when more than one marker is employed. Thus, information should be obtained on as many markers as possible. This conclusion is supported by observations presented which indicate that nuclear grade in combination with either or both of the receptors is a better predictor than either marker alone and that, as indicated by life table probability values and relative odds ratios, an increasing number of favorable tumor prognostic indicators results in a better patient outcome particularly in PFT-treated patients. A possible explanation is considered for why the separation of receptor/nuclear grade categories is more orderly and pronounced in PF-treated patients receiving tamoxifen than in those given PF alone.

Familial occurrence of breast cancer is associated with reduced natural killer cytotoxicity

Abstract: A factor in the incidence of spontaneous neoplasms in mice is the endogenous level of natural cell-mediated cytotoxicity (1, 2). These immunosurveillant or host defense mechanisms are probably under the control of multiple gene products (3, 4) including interferons. We studied natural killer (NK) cytotoxicity using peripheral blood mononuclear cells from 59 normal individuals with either a high (17) or low (42) familial incidence of breast cancer. The K562 cell line was used as target in51Cr release assays. Three effector: target ratios (6.2 : 1, 25 : 1, and 50 : 1) were studied in quadruplicate using 3, 4 and 5-h incubations. Significantly lower natural killer activity (p<0.002) was detected in normal individuals with high familial incidences of breast cancer compared to individuals with low incidences in each of the three separate assays (50 : 1). The same conclusion was reached whether the data were expressed in terms of lytic units per 107 blood mononuclear cells or as % specific51Cr released. Thus, a relationship was observed between the occurrence of breast cancer in closely related family members and low natural cell-mediated cytotoxicity. This result suggests that defects in NK activity may play a role in the initiation of human breast tumors. However, prospective studies will be necessary to establish whether low NK cell activity is a risk factor for breast cancer.

Antiestrogen action of progesterone in breast tissue.

Abstract: In normal breast, estrogen stimulates growth of the ductal system, while lobular development depends on progesterone. Thus, estrogen and progesterone, when secreted in an adequate balance, permit the complete and proper development of the mammary gland. Progesterone may also have an antagonistic activity against estradiol, mediated through a decrease in the replenishment of the estrogen receptor, and also through increased 17 beta-hydroxysteroid dehydrogenase which leads to accelerated metabolism of estradiol to estrone in the target organ. Thus, it can be inferred that long periods of luteal phase defect leading to an unopposed estrogen effect on the breast might promote breast carcinogenesis.

Menopausal estrogen use and the risk of breast cancer.

Abstract: The relationship between the occurrence of female breast cancer and menopausal estrogen replacement was investigated in a population-based case-control study. One hundred and eighty-three white female residents of King County, Washington (ages 50–74) in whom breast cancer was diagnosed from July, 1977, through August, 1978, were interviewed with respect to reproductive and other factors, with emphasis on the use of estrogen-containing medication. For purposes of comparison, the same data were collected from 531 white female King County residents of the same ages without breast cancer. Use of menopausal estrogens was reported somewhat more commonly among controls than among cases (relative risk = 0.74, 95% confidence interval = 0.51−1.08) and some variation in proportions of users was present between different hysterectomy-oophorectomy subgroups. However, each of these differences could easily have been due to chance. No substantial trends in risk were apparent with increasing duration of use, time since first use, time since last use, or average dose. The findings suggest that in King County no important relationship exists between use of menopausal estrogens and the occurrence of breast cancer.

Gonadotropin releasing hormone (GnRH) analogs for the treatment of breast and prostatic carcinoma.

Abstract: ’Superagonist’ analogs of GnRH produce a paradoxical inhibition of gonadotropin secretion when given on a long-term basis, and may well produce a more complete ’medical oophorectomy’ than antiestrogens in premenopausal breast cancer patients. Here we review the background and pharmacology of these agents, together with the experience of their use with prostate cancer and early trials in breast cancer. Their effectiveness without significant toxicity, together with new biodegradable implants for their easily acceptable long-term administration, suggest that a highly selective medical means of fully inhibiting ovarian estrogen production is now available for more extensive trials in breast cancer patients.

Adjuvant tamoxifen in postmenopausal breast cancer: preliminary results of a randomized trial.

Abstract: Between May 1978 and March 1982, 179 postmenopausal women with operable breast cancer were randomized to receive either adjuvant tamoxifen, 40 mg daily for three years (TAM group), or no further treatment (controls). The difference in five-year survival rates (61% in the control group, 72% in the TAM group) was not statistically significant. However, there was a significant improvement in disease-free survival in the TAM group (61%) relative to the controls (44%) (p = 0.008). In estrogen receptor positive patients, tamoxifen improved both the disease-free rate (47% controls, 80% with tamoxifen) and the survival rate (63% to 83%). Similar results were observed in progesterone receptor positive patients. In patients that were estrogen receptor negative, tamoxifen modified neither the survival rate nor the disease-free interval.

Steroid hormone receptors as prognostic indicators in primary breast cancer.

Abstract: Recurrence-free survival (RFS) has been evaluated with regard to estrogen and progesterone receptor (ER and PgR) status for 145 postmenopausal women with primary breast cancer at high risk for recurrent disease. All patients received only local-regional therapy as an adjuvant therapy (DBCG protocol 77-c patients). ER+ patients had a significantly longer RFS than ER-patients. This difference was apparent using a cut-off level of 10 fmol/mg cytosol protein to distinguish between ER+ and ER-patients. There was no apparent difference in patients with high (greater than = 100 fmol/mg cytosol protein) ER levels vs. those with intermediate (10-99 fmol/mg cytosol protein) levels, indicating that the prognostic value of ER determinations in the natural course of the disease resides in a qualitative rather than a quantitative distinction among patients. No difference in RFS was found patients when patient were subdivided according to PgR status. The clinical applicability of the ER-ICA assay method for ER determinations is demonstrated in a subset of patients, some of whom received adjuvant endocrine therapy.

Combined endocrine treatment of postmenopausal patients with advanced breast cancer. A randomized trial of tamoxifen vs. tamoxifen plus aminoglutethimide and hydrocortisone.

Abstract: The therapeutic efficacy of combined endocrine therapy with tamoxifen, aminoglutethimide and hydrocortisone (T+AG+H) was evaluated against treatment with tamoxifen (T) alone in 210 patients above 65 years of age with metastatic breast cancer. The treatment results have been assessed for the 166 fully evaluable patients and were the following for the T and T+AG+H groups, respectively: PD: 31 and 35%; NC: 35 and 37%; PR: 13 and 16%; and CR: 21 and 12%. The overall treatment results are not statistically different (p = 0.35) and the 95% C.L. of the difference of the response rates are -8% to +20%. The median duration of remission was approximately 24 months in both treatment groups (p = 0.31). The time to treatment failure was comparable with median values of 10 and 8 months in the T and the T+AG+H groups respectively (p = 0.17). Toxicity was more frequent and severe in the combined treatment group and could in most instances be attributed to treatment with AG+H. In conclusion, the simultaneous use of T and AG and H does not seem to improve the therapeutic results in postmenopausal patients with advanced breast cancer.

Transferrin receptor is inversely correlated with estrogen receptor in breast cancer.

Abstract: The transferrin receptor (TfR) has been identified as a marker for proliferation in cells in culture and can be accurately quantitated by specific radioimmunoassay. This study directly quantifies levels of TfR and compares them to levels of estrogen receptor (ER) and progesterone receptor (PgR) in biopsy material obtained from patients with infiltrating ductal carcinoma of the breast. A comparison of ER and TfR levels displayed an exponential distribution which was log-normalized to yield a linear inverse relationship (r = −.44). Although ER was strongly correlated with PgR, there was no correlation pattern between TfR and PgR. Multiple regression analysis indicated that 73% of ER levels could be predicted by a combination of the other two markers, PgR (representing degree of differentiation) and TfR (representing growth rate). Transferrin receptor levels were also found to be correlated (p<.05) with menopausal status, with tumors from premenopausal patients exhibiting higher levels, whereas the opposite pattern was shown for estrogen receptor levels (p<.02). Neither steroid receptor nor transferrin receptor levels were correlated to stage of disease or presence of nodal involvement. Addition of TfR level as an independent marker for proliferation may facilitate the decision-making process in the treatment of individual cases of carcinoma of the breast.

Adrenal steroids stimulate growth and progesterone receptor levels in rat uterus and DMBA-induced mammary tumors.

Abstract: We have studied the effect of treatment with the adrenal steroids androst-5-ene-3β,17β-diol (Δ5-diol) and dehydroepiandrosterone (DHEA) on the growth and progesterone receptor levels of dimethylbenz-(a)anthracene (DMBA)-induced mammary tumors in the rat.

A comparison of static cytofluorometry and flow cytometry for the estimation of ploidy and DNA replication in human breast cancer.

Abstract: 332 primary invasive breast carcinomas were analysed by static cytofluorometry and flow cytometry. The ploidy distributions were similar, and 54% of the tumors were judged DNA aneuploid by both methods. The coefficient of variation of the G0–G1 peaks ranged from 2.0 to 8% with both techniques, but the mean was somewhat lower with flow cytometry — 4.1%, compared to 4.9% for the static measurements. The proportion of S-phase cells was possible to estimate from 80% of the flow histograms and 70% of the static histograms. S-phase was not estimated from the static histograms if less than 150 tumor cells were measured. With 160 tumors S-phase was measured by both methods. The range was 0 to 27% with the static measurements and 0.7 to 25% with flow cytometry. Corresponding mean values were 7.6% and 8.2%, which are similar to thymidine labeling index results with breast cancers reported in some studies. A close correlation was obtained (r = 0.927) comparing S-phase fractions estimated from aneuploid tumors with flow cytometry and static cytofluorometry if more than 200 cells were measured with the latter. The proportion of S-phase cells was significantly lower for the diploid tumors. We conclude that both techniques can be useful for the estimation of DNA ploidy and replication in human breast cancer.

Sensory changes after treatment of operable breast cancer.

Abstract: A study has been conducted to compare the nature and severity of post-operative sensory changes (sensory loss, paraesthesiae, and pain) among patients with breast cancer treated by either modified radical mastectomy or a conservative procedure (tumourectomy, axillary clearance, iridium implant, and external radiotherapy) There was a similar incidence of post-operative sensory loss in the two groups, reported by 82% of the mastectomy group and 77% of the iridium group, and an equivalent rate of improvement (76 and 80% respectively) Post-operative paraesthesiae occurred in 61% of the mastectomy group and 63% of the iridium group; maximum severity of paraesthesiae was similar as was the percentage improving Among the mastectomy group 55% reported phantom breast sensation and 61% of the iridium group had post-operative breast pain Improvement occurred in 58% of those with breast pain These findings may have implications for the counseling of patients with breast cancer who are going to be treated by certain conservative procedures

Class distribution of immunoglobulin-containing plasma cells in the stroma of medullary carcinoma of breast.

Abstract: A class distribution of plasma cells associated with the stroma in twenty-eight cases of medullary carcinoma of the breast was investigated by an unlabeled immunoperoxidase method. The stroma of the medullary carcinomas tested was found to contain predominantly IgG plasma cells except in two cases. Stroma of the other types of breast carcinoma, including ten cases of papillo-tubular carcinoma, five cases of scirrhous carcinoma, and six cases of medullary tubular carcinoma, contained predominantly IgG plasma cells, although few plasma cells were associated with carcinoma tissues in the latter group. Plasma cells associated with control specimens, including normal breast, fibroadenoma, cystic disease, and intraductal papilloma, were found to be predominantly of IgA type. Few carcinomatous epithelial cells contained secretory components in the cytoplasm, while a number of cells positive for secretory components were observed in acinar and ductular epithelia of normal breast tissues and in benign proliferative lesions of the breast. It is suggested that the lymphoid cells infiltrating the stroma of medullary carcinoma represent a sign of host immune response against the carcinoma cells which is related to the well-known favorable prognosis associated with this tumor.

A comparison of tumor-related antigens in male and female breast cancer.

Abstract: A retrospective analysis was undertaken in which 15 female and 15 male breast cancers were matched by age, stage, estrogen receptor status, and histologic type. Our protocol compares male and female breast cancers for reactivity with antibodies against tumor-associated antigens known to be present on female breast cancer cells. Formalin-fixed sections of each primary tumor were reacted in the ABC immunoperoxidase assay against antibodies B72.3 and DF.3 and an antibody to theras p21 antigen. Reactivity to B72.3 and DF.3 was similar. However, the ras p21 antigen was expressed to a significantly greater extent in female breast cancers (p = .0008). Thus, although there are similarities in antigenic phenotype of male and female breast cancers, some female breast cancers may have a different pathogenesis as demonstrated by increased amounts of a specific oncogene product.

Influence of hormones on DNA synthesis of breast tumors in culture.

Abstract: Tissue culture techniques have been developed for studying the influence of hormones on human breast tissues. The present study demonstrated that estrogen induced a highly significant increase in3H-thymidine incorporation into DNA and labelling index of ductal epithelium of fibrocystic disease; there was no effect of progesterone, either alone or in combination with ovine prolactin, on benign lesions. Estrogen stimulated certain malignant tumors derived from postmenopausal women. These studies also showed that there was an inhibitory effect of3H-thymidine incorporation into DNA by the effect of progesterone on malignant lesions. When menopausal status was considered, it was found that DNA synthesis was significantly higher in the presence of insulin and hydrocortisone in malignant tumors derived from premenopausal women than from postmenopausal women, or than in benign lesions. Thus, the present findings may provide evidence that specific activity may be an important measurement for breast tumor DNA synthesis in response to ovarian hormones or other substances.

Prognosis in node-negative breast cancer.

Abstract: In a selected group of 207 breast cancer patients with tumor-free axillary nodes, clinical and pathological features were evaluated as to their relationship to long-term disease-free survival. No clinical feature was found to be prognostically useful. Of pathologic features studied, four appear to have significance. These are (1) the volume of the primary mass, (2) the histologic or nuclear grade, (3) the presence of invasive lobular carcinoma in the primary mass, and possibly (4) the presence of neoplastic cells in intramammary lymphatic vessels. When two or more of these four features are present, prognosis is less favorable than when there is only one, but the influences are not arithmetically additive.

Aromatase inhibitors for treatment of breast cancer: current concepts and new perspectives.

Abstract: Estrogens provide the major hormonal support for endocrine-dependent human mammary neoplasms. In postmenopausal women, the extraglandular aromatization of the adrenal prehormone, androstenedione to estrone is the major pathway for estrogen biosynthesis. Estrone can then be converted into estradiol or into an inactive conjugate, estrone sulfate. Recent data suggest that the estrogens may also be synthesized in situ by human breast tumors, either from androstenedione via aromatase, or from estrone sulfate via the enzyme, sulfatase. Our enzyme kinetic studies support the predominance of the sulfatase pathway for in situ estrogen biosynthesis. The ability of estrone sulfate to stimulate colony formation of the nitrosomethylurea-induced rat mammary tumor in the clonogenic assay, suggests that this in situ pathway has biologic relevance. Aromatase inhibitors can be used to suppress the levels of circulating estrone, estrone sulfate, and estradiol in postmenopausal women. Aminoglutethimide, the major inhibitor currently used clinically, acts in a competitive fashion and blocks cholesterol side chain cleavage and 11 beta-hydroxylase as well as aromatase. Clinical studies indicate that the combination of aminoglutethimide plus replacement glucocorticoid causes breast tumor regression with the same frequency and for the same duration as surgical ablative therapies such as adrenalectomy or hypophysectomy. Aminoglutethimide also induces a similar rate of tumor regression as achieved with the antiestrogen, tamoxifen. However, because tamoxifen is associated with fewer side effects, this antiestrogen is to be preferred over use of aminoglutethimide as first-line hormonal treatment for women with breast cancer. Several specific suicide inhibitors of aminoglutethimide such as 4-hydroxy-androstenedione are being developed and have proven effective in early clinical trials with breast cancer patients. Further development of active aromatase inhibitors should allow precise control of estradiol levels in women with breast cancer. This ability to perform an 'estrogen clamp' may allow new strategies to be developed in which hormone depletion followed by repletion can produce a synchronization of tumor cell DNA synthesis. If achievable, such manipulations may allow potentiation of the effects of cytotoxic chemotherapy. This latter concept is currently being rigorously tested in basic and in clinical investigative studies.