Impact of menopausal hormone-replacement therapy on clinical and laboratory characteristics of breast cancer

In response to the General Medical Council's initiative to reform UK medical undergraduate education only a minority of medical schools have developed entirely novel curricula. Although the experiences gained by these schools in curriculum design and planning have not been recorded in the literature they are likely to be of interest to other medical schools still contemplating course revision. The medical school at the University of Liverpool recently launched an integrated problem-based course differing radically from its predecessor. The General Medical Council considered integration of contributing disciplines one of the most important aims of reform, yet courses that integrate independent component disciplines may be perceived by staff as threatening due to the loss of structure and disciplinary autonomy. Strategies for early course development must take account of these concerns as well as dealing with the identification of course content. A multidisciplinary consensus group process, designed to combat some of these problems, was employed to identify the learning objectives and core content for the new course. The purpose of this paper is to describe, first, the processes employed to identify the core palliative care component for a new PBL curriculum and secondly, how these objectives were integrated horizontally and vertically throughout all course elements.     

Does post-menopausal hormone-replacement therapy increase risk for breast cancer? A perspective on the findings of the Nurses'' Health Study

With the onset of science-based medicine in the mid-19th century, environmental factors were almost totally discarded as health determinants. This was a complete rupture with the medical thinking which had prevailed since the time of Hippocrates. Yet, for the vast majority of mankind, harmony with environmental reality remains the most important determinant of good or ill health. This scission explains to a great extent the differences between traditional and Western medicine, which are based on entirely different concepts and on distinct paradigms. Environment as a health determinant--in its broadest definition to include both physical and social environments--is again being considered of importance as a result of better understanding of causality factors, and because of the influence of disciplines such as ecology and epidemiology. Here we show that human societies can develop different methods of adjusting to their environments, some of which would increase the risks of disease and others which can be considered as resistance factors of a social nature. Societies and individuals alike are not equal in relation to health risks.     

Lipoprotein(a) and the cardiovascular risk during estrogen-progestin replacement therapy in postmenopause

A homogeneous group of 37 patients, aged between 52 and 61 years was considered in relationship to the metabolic response during hormonal replacement therapy (HRT). A free endocrinological-metabolic pathology control group, formed by 40 patients, who were not treated with any therapy, was also considered. Study-trial was comprehensive of a 123 months follow-up, with some periods of study at 0, +6, +12 months. Metabolic responses of lipoprotein(a) and apolipoprotein A and B during the different follow-up steps were determined. Total and fractioned cholesterol and triglycerides were also determined. Significant correlations were shown between Lipo(a) and Apo B and also between Lipo(a) and LDL in both groups considered Lipoprotein(a) was determined by ELISA methodic and turbidimetric methodic. The aim of our study was to verify the importance of the new markers of the atheromatous risk. The reduction of lipoproteins middle value observed in the HRT group shows a little, but however present, estrogens action to the Lipo(a) itself. This fact testifies to the benefit of the use of HRT in post-menopause also as reg ards an evaluated cardiovascular risk inhibition.     

The mammographic aspect and the prognosis of breast carcinoma

The authors report on 354 consecutive cases of invasive breast carcinoma followed up 3 to 13 years. The prognostic value of the mammographic appearance of cancer, determined according to Broberg, was studied, as well as that of other indicators, such as pT, pN and estrogen receptor content. An association was found between the mammographic appearance and the other prognostic indicators, but such an association was at the limits of statistical significance (pT p = 0.033, pN p = 0.039, ER p = 0.033) and the mammographic patterns associated with more favorable indicators were not consistent across the three variables. Ten-year actuarial overall survival was significantly associated with pT (p < 0.0001), pN (p < 0.0001) or estrogen receptor content (p < 0.001), but not with mammographic appearance. Multivariate analysis confirmed such results. We found no evidence, as suggested in some literature reports, of any association of the mammographic appearance of breast cancer with survival, and we believe that this indicator has no practical use in predicting prognosis in breast cancer patients.     

Metaplastic carcinoma of the breast: mammographic appearance with pathologic correlation

OBJECTIVE: The objective of this study was to describe the mammographic appearance with pathologic correlation of metaplastic carcinoma of the breast. CONCLUSION: Metaplastic carcinomas of the breast are masses with mammographic characteristics of low suspicion because of their histologic appearance. Metaplastic carcinoma should be included in the differential assessment of predominately circumscribed, noncalcified masses revealed on mammography. One salient feature that may distinguish metaplastic carcinomas is the occurrence of a circumscribed portion with a spiculated portion, which is seen in carcinomas that have a significant mixture of metaplastic and invasive carcinoma growth patterns.     

CT appearance of the normal and abnormal breast with mammographic correlation

Mammography is the preferred technique to evaluate the breast but computed tomography (CT) performed for extramammary disease often images breast tissue. We reviewed studies of patients who underwent both CT and mammography to identify abnormalities that were visible with both techniques. The CT appearance of the normal breast, breast cancer, and several other abnormalities is demonstrated in this study. CT may occasionally allow for a precise diagnosis of a previously unsuspected breast lesion but a mammogram is usually required.     

Stereotactic fine needle aspiration in the management of mammographic abnormalities detected in breast screening

BACKGROUND: Fine needle aspiration (FNA) is used routinely in the management of palpable breast lumps; with the implementation of the stereotactic technique its use has been extended to the investigation of mammographic abnormalities. The advent of breast screening means that many mammographic abnormalities will be detected; because routine open biopsy is impractical and undesirable, stereotactic fine needle aspiration becomes the method of choice for investigation. METHOD: Within a 28 month interval, 81 Chinese women underwent stereotactic FNA in Kwong Wah Hospital, Hong Kong. RESULTS: Fifty-one women (62.9%) had a benign cytology result and no further investigations were required. Inconclusive results were obtained in 18.6% of the aspirates. Open biopsy was required in 16 women (19.8%). CONCLUSION: Stereotactic FNA is very useful in the exclusion of malignancy and the avoidance of open biopsy in asymptomatic women who have mammographic abnormalities.     

Adenoid cystic carcinoma of the breast: mammographic appearance and pathologic correlation

OBJECTIVE: The objective of our study was to describe the mammographic features of adenoid cystic carcinoma of the breast and to correlate mammography findings with histopathologic findings. CONCLUSION: Adenoid cystic carcinoma is a rare type of breast neoplasm that usually appears as a slowly enlarging nodule. In spite of its low incidence, recognition is important because early detection ensures good prognosis. On mammography, these tumors often appear as moderately circumscribed, lobulated nodules that are similar to other types of benign and malignant tumors. Therefore, cytologic and histologic evaluations are needed for accurate diagnosis.     

A prospective evaluation of dermatological side-effects during alpha-interferon therapy for chronic viral hepatitis

OBJECTIVE: Alpha-interferon therapy may occasionally account for immune-mediated phenomena. This study was conducted in an attempt to investigate the incidence of the development of immune-mediated dermatological diseases during alpha-interferon therapy in patients with chronic viral hepatitis. The latter has not been evaluated prospectively, whereas most of the previous studies examined small numbers of interferon treated patients or consisted of case reports. DESIGN: A prospective case-control study. SETTING: A tertiary referral centre. PARTICIPANTS: One hundred and twenty consecutive patients with chronic viral hepatitis (67 with hepatitis B, 45 with hepatitis C, six with both hepatitis viruses, and two with delta hepatitis) were evaluated during a course of alpha-interferon therapy. In addition, 120 consecutive patients with chronic liver diseases (disease control group), who had never received alpha-interferon therapy, were evaluated during the period of the study (at least for 12 months). INTERVENTIONS: Recombinant alpha-interferon at a dose of 4.5 or 5 million units subcutaneously (s.c.) three times per week for 6 to 12 months was administered to patients with hepatitis B. The patients with chronic hepatitis C were treated with 3 million units s.c. three times per week for 12 to 18 months. The patients with chronic hepatitis B and C infections received 4.5 million units for 6 months, and then 3 million units for an additional 6 to 12 months. Finally, the patients with chronic delta hepatitis received 5 million units for 1 year or more. MAIN OUTCOME MEASURES: To assess prospectively the incidence of these dermatological disorders during alpha-interferon therapy and to estimate if there is any relationship between their development and the clinical, laboratory or other characteristics of the patients with chronic hepatitis. RESULTS: Three to 6 months after the initiation of alpha-interferon three patients with chronic viral hepatitis (two with hepatitis C and one with hepatitis B) developed lichen planus, whereas one patient with hepatitis C developed relapsing aphthous stomatitis. The development of these disorders was significantly associated only with the presence of antinuclear antibodies before the initiation of alpha-interferon (P=0.000000). None of the patients from the disease control group had such a manifestation during the follow-up. Lichen planus resolved after the end of therapy in all of them. In contrast, therapy was discontinued in the patient who developed aphthous stomatitis, owing to the painful lesions. CONCLUSIONS: This study demonstrated that alpha-interferon may rarely (3.3%) induce immune-mediated dermatological disorders, especially lichen planus. The development of these disorders may reflect a subclinical or covert autoimmune background of patients, as suggested by the presence, although in low titres, of antinuclear antibodies. However, when lichen planus developed, it was mild, did not require the discontinuation of therapy and resolved after alpha-interferon administration had ceased.     

Analysis of mammographic density and breast cancer risk from digitized mammograms

To evaluate the association between mammographic density and breast cancer risk, a simple, observer-assisted technique called interactive thresholding was developed that allows reliable quantitative assessment of mammographic density with use of a computer workstation. Use of this technique helps confirm that mammographic density is one of the strongest risk factors for breast cancer and is present in a large proportion of breast cancer cases. The strong relationship between mammographic density and breast cancer risk suggests that the causes of breast cancer may be better understood by identifying the factors associated with mammographically dense tissue and determining how such tissue changes as these factors vary. Furthermore, because it can be modified, mammographic density may also be a good vehicle for the development and monitoring of potential preventive strategies. Areas of ongoing investigation include evaluating a potential genetic component of mammographic density by comparing density measurements in twins and understanding changes in density relative to age, menopausal status, exogenous hormone use, and exposure to environmental carcinogens. In addition, work is ongoing to establish measurements from imaging modalities other than mammography and to relate these measurements directly to breast cancer risk.     

Contextual variations in implicit evaluation.

In the present research, the authors examined contextual variations in automatic attitudes. Using 2 measures of automatic attitudes, the authors demonstrated that evaluative responses differ qualitatively as perceivers focus on different aspects of a target's social group membership (e.g., race or gender). Contextual variations in automatic attitudes were obtained when the manipulation involved overt categorization (Experiments 1-3) as well as more subtle contextual cues, such as category distinctiveness (Experiments 4-5). Furthermore, participants were shown to be unable to predict such contextual influences on automatic attitudes (Experiment 3). Taken together, these experiments support the idea of automatic attitudes being continuous, online constructions that are inherently flexible and contextually appropriate, despite being outside conscious control. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

State variations in the newborn and mother–infant interaction during breast feeding: Some sex differences.

30 male and 33 female newborns were observed being breast-fed in the maternity ward. The conditional probabilities of various maternal and infant behaviors were studied when the infant was in 1 of 4 states: asleep, drowsy, fussy, and crying. Although male dyads showed more interactive activity on the asleep end of the scale, female dyads showed more interactive activity on the awake end of the scale. These interaction episodes were characterized by greater physical proximity in male dyads and more social interaction in female dyads. Although male neonates spent less time than females in the fussy state, when they were in this state, they seemed to be more agitated than the females. A relatively high proportion of simultaneous vocalization was observed in dyads of both sexes during the fussy state. Results are qualified by the great individual differences observed among the neonates in the amount of time spent in each of the states. (15 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ductal carcinoma in situ of the breast: correlation of pathologic and mammographic features with extent of disease

Optimal treatment of ductal carcinoma in situ (DCIS) of the breast requires an improved understanding of its pathologic extent and propensity for local recurrence. This study was performed to analyze mammographic and pathologic features of DCIS that might predict the extent of disease within the breast and facilitate treatment selection between lumpectomy alone, lumpectomy and radiotherapy, and mastectomy. At our institution, 60 cases of DCIS were diagnosed in 59 patients from June 1985 to February 1995 and form the basis of this retrospective study. Demographic and treatment-related information was obtained from hospital and tumor registry records. Mammograms were reviewed and size estimates of the abnormalities were determined. Pathologic slides from all cases were reviewed and classified according to size group, focality, nuclear grade, necrosis, and histologic subtype. DNA ploidy status and proliferation indices were available for 28 patients. Pathologically, 43 (72%) cases were < 15 mm, 14 (23%) were 16 to 40 mm, and 3 (5%) were > 40 mm. Five (8%) of the lesions were multicentric, 28 (47%) focal, and 27 (45%) multifocal. Thirty-three (55%) patients were treated by mastectomy, 16 (27%) by lumpectomy alone, and 11 (18%) by lumpectomy and radiation therapy. Mammographic size, histologic grade, presence or absence of necrosis, histologic subtype, DNA ploidy, and proliferative index were compared with pathologic size and focality by chi 2 analysis. Mammographic size correlated significantly with pathologic size (chi 2 = 11.3; P = 0.02) but underestimated the extent of disease in 9 cases. Although focality correlated significantly with pathologic size (chi 2 = 15.8; P = 0.003), the remaining histopathologic features did not significantly correlate with pathologic size or focality. Histopathologic features, including DNA studies, do not reliably predict the pathologic extent of DCIS, but mammographic size and focality do significantly correlate with pathologic size. Nevertheless, most cases of DCIS are small focal or multifocal lesions that are amenable to breast conservation approaches; further studies are needed to determine the appropriate use of lumpectomy, radiation therapy, and mastectomy in the treatment of DCIS.     

Quantitative evaluation of the cardiovascular risk associated with hormone substitution therapy during menopause

The cardiovascular risk of postmenopausal hormone replacement therapy is a controversial subject. A quantitative evaluation of 12 studies of cohorts show a global relative risk of major ischemic cardiac disease of 0.69 (95% confidence interval: 0.60-0.79) in women having or having had oestrogen therapy compared with women who have never taken this treatment. This relative risk was 0.94 (95% confidence interval: 0.77 to 1.15) for stroke and 0.80 (95% confidence interval: 0.65-0.97) for cardiovascular mortality. These results are coherent with the hypothesis of a protective effect of oestrogens against coronary artery disease in postmenopausal women. However, they cannot be generalised to hormone replacement therapy usually proposed in France. The influence of an association of oestrogen-progesterone therapy and the effects of administering oestrogens by an extra-gastrointestinal route on vascular risk are unknown. Randomised clinical trials are needed to determine the effects of postmenopausal hormone replacement therapy on athero-thrombotic disease.     

Endoscopic surveillance of Barrett's esophagus: a cost-effectiveness comparison with mammographic surveillance for breast cancer

OBJECTIVE: Endoscopic surveillance of Barrett's esophagus is commonly practiced to detect malignancy in an early and curable stage. However, the cost-effectiveness of this practice has been questioned. To clarify this issue, we undertook a cost analysis of endoscopic surveillance to detect adenocarcinoma in Barrett's esophagus compared with mammography used to detect occult carcinoma of the breast, a widely accepted cancer surveillance technique. METHODS: The rate of esophageal adenocarcinoma detected by endoscopic surveillance was calculated for Duluth Clinic patients with Barrett's esophagus seen from 1980 to 1995 and compared with published rates. The rate of occult breast cancer detection was calculated for all women undergoing surveillance mammography at the Duluth Clinic for the year 1994 and compared with published rates. Costs for screening studies and therapy for cancer treatment for both cancers were calculated based on clinical results and assumptions regarding outcomes derived from published reports, and the costs were compared. RESULTS: Endoscopic surveillance of 149 patients with benign Barrett's esophagus was performed for a total of 510 patient-yr, during which time seven patients developed adenocarcinoma, an incidence of one case per 73 patient-yr of follow-up. Occult breast cancer was detected in 50 of 12,537 mammograms, a detection rate of 0.4%. The incidences in both cases were comparable to published figures. The costs of detecting a case of adenocarcinoma in Barrett's esophagus and occult breast cancer were $37,928 and $54,513, respectively, and those for treatment resulting in cure were $83,340 and $83,292. Cost per life-yr saved was $4,151 for adenocarcinoma in Barrett's esophagus and $57,926 for breast cancer. CONCLUSION: Endoscopic surveillance of patients with Barrett's esophagus compares favorably with the common practice of surveillance mammography to detect early breast cancer, and should therefore be considered to be as cost-effective as surveillance mammography.