Authorization of anastrazole to prevent breast cancer in postmenopausal women: a bad idea.

Anastrazole has recently been approved for the prevention of breast cancer in high-risk women in the UK. When given to high-risk women anastrazole halves the risk of developing breast cancer but doesn't reduce the risk of breast cancer death and is associated with significant harms. Women need to be counselled about both the benefits and risks associated with anastrazole use to enable an informed treatment choice.

Chains of evidence, mosaics of data: does estrogen 'cause' breast cancer? How would we know?

There appears to be a broad consensus that estrogen is a cause of breast cancer. Proof of cause and effect in clinical medicine requires a different approach for an epidemiological exposure (a 'mosaic' approach) than for an infectious agent suspected of causing a particular disease (a 'chain of evidence' approach). This paper discusses the differences between these two approaches in determining the relationship between a risk factor and a disease, and assesses the strength of the data linking estrogen with breast cancer. Analysis of existing data, including findings from the Women's Health Initiative, finds that all nine of the criteria necessary for confirming the epidemiological strength of a risk factor are not met in the case of estrogen, raising serious questions about the validity of this widespread assumption.

What are the real risks for breast cancer?

There is a steady drumbeat of peer-reviewed medical articles relating risks of breast cancer from a variety of factors. Whether or not the reported factors are under the control of any given individual, they have been trumpeted by the lay media and are responsible for the understandable finding among women that breast cancer generates more anxiety than heart disease, even though the number of US women who died of heart disease in 2010 is over seven and a half times the number who fell victim to breast cancer. This article attempts to reduce the anxiety-inducing barrage of these reports by orienting physicians to better understand the validity of reported breast cancer risk factors. We hope to provide this understanding by: explaining the difference between relative and absolute risk, encouraging application of the 95% confidence interval to better evaluate the statistical validity of any given risk factor; placing the reported risk factors in the context of an accepted risk factor like cigarette smoking and lung cancer; and communicating the limits of statistical validity in the absence of reproducibility. This review will, to a small degree, provide a balance to the reports currently dominating the literature.

Syngeneic marrow transplantation in patients with multiple myeloma.

Eleven patients with advanced multiple myeloma (MM) received syngeneic marrow (n = 10) or peripheral blood stem cell (n = 1) transplants following cyclophosphamide (CY) and total body irradiation (TBI) (n = 8), busulfan (Bu) and CY (n = 1), Bu, CY and TBI (n = 1) or Bu, melphalan and thiotepa (n = 1). At the time of transplant one patient had stage II and 10 patients had stage III disease. Four patients had refractory disease, two had chemotherapy sensitive disease and five had progressed after an initial response to chemotherapy. The median time from diagnosis to transplant was 353 days (range 176-6118). After transplant, the median time to achieve granulocytes of 0.5 x 10(9)/l and platelets of 20 x 10(9)/l was 12 days (range 9-20) and 12 days (9-27), respectively. One patient died of interstitial pneumonia syndrome on day 32 and one died of veno-occlusive disease of the liver on day 44 post-transplant, and these were unevaluable for response. Five of nine evaluable patients achieved a complete response (CR), three a partial response, and one patient had no response. Three patients who did not achieve CR died of progressive disease 106, 142 and 321 days post-transplant. Of five patients who achieved a CR, three relapsed on days 539, 737 and 1706 and died on days 1759, 1596 and 1736, respectively; one patient died of myelodysplastic syndrome on day 1407 without evidence of MM and one patient is alive and disease-free 3297 days after transplant. One of the two long-term survivors has a persistent monoclonal protein in the blood 15 years post-transplant. These data show that high-dose therapy and infusion of normal syngeneic marrow cells can cure a small fraction of patients with MM. However, the majority of patients did not achieve durable CR, demonstrating the need for improved transplant conditioning regimens, earlier transplant or additional post-transplant treatment strategies when syngeneic transplants are performed.

Menstrual influence on surgical cure of breast cancer.

In a retrospective study of 44 premenopausal women who underwent resection of a primary breast cancer and were followed for 5 to 12 years, disease recurrence and metastasis were more frequent and more rapid in women who had been operated upon during the perimenstrual period (days 0-6 and 21-36 of the menstrual cycle). By multivariate analysis, the time of resection in relation to the menstrual cycle is an independent predictor of the likelihood of future metastatic disease. Patients who underwent resection during the perimenstrual period had a more than quadrupled risk of recurrence and death compared with women operated upon during days 7 to 20 of the menstrual cycle.

Cataracts induced by intermittent Decadron used as an antiemetic.

Recent reports have shown that Decadron (dexamethasone; Merck Sharp & Dohme, West Point, Pa) has a significant antiemetic effect on cisplatin-induced vomiting. Although the development of posterior subcapsular cataracts is a known complication of systemic steroid therapy, it usually occurs after several years of chronic administration. A young diamond dealer developed visual impairment attributed to bilateral posterior subcapsular cataracts following only four courses of intermittent Decadron used as part of a five-drug antiemetic regimen for cisplatin-associated nausea. This report is intended to alert others to the possible development of this serious complication following short-term Decadron therapy.

Illness-related and treatment-related factors in psychological adjustment to breast cancer.

Seventy-eight breast cancer outpatients were interviewed and their medical records were reviewed to document illness-related and treatment-related factors associated with psychosocial adjustment. Poor prognosis and more radical surgery both independently predicted poor psychological adjustment. The effect of type of surgery appeared to be mediated by the patient's sense of disfigurement and by changes in the sexual and affectional patterns in the marriage, rather than by prognosis or disability. Degree of dysfunction and whether or not the patient had radiation therapy or chemotherapy had no independent effects on psychological adjustment. Results point to the problematic psychosocial outcomes associated with mastectomy and, more generally, to the illness- and treatment-related factors that may place a breast cancer patient at risk for psychosocial adjustment problems.

Breast self-examination among diagnosed breast cancer patients.

The practice of breast self-examination (BSE) was explored by personal interview in a sample of women with diagnosed breast cancer. Despite physician recommendations to practice BSE, only 43% of those interviewed were examining themselves regularly, a figure that is little different from that of the general population. Predictors of BSE were age (older women were less likely to practice) and practice of BSE before diagnosis. Factors contributing to nonpractice were judged to be: (1) the patients' beliefs that occasional examinations by physicians are a sufficient substitute for BSE; (2) the patients' perceptions that BSE is discretionary and not truly "medical"; and (3) the fact that BSE may raise patients' anxiety over cancer without affecting its likelihood. It was concluded that the practice of BSE among diagnosed patients could be increased if physicians stress its importance and provide systematic instruction or reinstruction in its practice.

Treatment of primary breast cancer without mastectomy. Review of the literature.

During the 54-year period between 1927 and 1981, at least 4,290 patients with breast cancer treated with lumpectomy and/or radiotherapy as the primary therapeutic modality have been described. In all but two of the 24 reported studies, survival rates, even to 30 years, were similar to those of patients treated with variations of radical mastectomy, and the cosmetic result following treatment that preserved the affected breast was judged good to excellent by 81 to 85 percent of the patients so treated. The two exceptions were both in series of patients treated with doses of radiation known to be inadequate by current standards. We all have the responsibility of offering our patients the most effective treatment available with the fewest possible short-term and long-term side effects. This goal requires a constant, careful reevaluation of our treatments and results, as well as an open mind. According to available data, the combination of lumpectomy, axillary node dissection, external beam radiotherapy and iridium implant constitutes an acceptable alternative to mastectomy as treatment for primary cancer of the breast.

Angioimmunoblastic lymphadenopathy with dysproteinemia. A pathogenetic link between lymphoid proliferation and malignant lymphoma.

Two patients with angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) were studied. Both patients had marked increases in all three major immunoglobulin classes, and both lacked suppressor cell activity in vitro. These findings are consistent with the theory that AILD is a defectively regulated immune response to an unidentified antigen(s) and could provide clues to the pathogenesis of other lymphoproliferative disorders as well.

Cancer: the eighth plague--a suggestion of pathogenesis.

The current treatment of cancer is based on the assumption that this disease is the result of autonomous clonal proliferation of aberrant cells which must be excised, irradiated or selectively poisoned to achieve a cure. The presumption that the malignant cell constitutes the disease is now challenged by a variety of clinical observations and experimental studies. Like the grasshopper, which is transformed into a locust under altered environmental conditions, the cancer cell may be the manifestation of a defect in homeostatic regulation of cellular proliferation. Identification of the specific regulatory defect could allow for a more rational and more effective treatment of cancer in man.

Diagnostic planning using computer assisted decision-making for patients with Hodgkin's disease.

A family of computer programs has been developed to help physicians effectively utilize available clinical information as in indicator of tumor extent for the staging of Hodgkin's disease patients. Decision analysis techniques were employed to suggest chronologic sequencing of selected, risk-associated tests, tailored to the individual patient, that minimize the risk of iatrogenic mortality. These quantitative techniques provide an objective measure of expected survival for a given plan of action. By using this information a physician and patient can balance expected survival vs morbidity of proposed staging procedures. Physicians can then focus on the interrelation between the inherent diagnostic uncertainty, therapy-induced expected survival, and morbid consequences of staging procedures. The use of these decision-making tools enables the physician to identify patient-specific presentations where the formation of an individual diagnostic plan could lead both to reduction in testing and to an increased survival rate.

Decision analysis to evaluate lymphangiography in the management of patients with Hodgkin's disease.

We used decision analysis to explore the role of lymphangiography for staging Hodgkin's disease. Factors included were status of the patient before the test, accuracy and mortality of lymphangiography, mortality of laparotomy and effectiveness of selected treatment. We analyzed hypothetical cases with varying probabilities being in Stages I+II, III and IV to determine the population in which indication for laparotomy would depend upon results of lymphangiography. Calculations made for asymptomatic patients revealed that the diagnostic usefulness of lymphangiography is restricted to patients either with a relatively low probability of Stage IV or with a very high probability of Stage IV disease. This population is further restricted as false-positive and false-negative results of lymphangiography increase.