Francine Halberg

American Society of Clinical Oncology 2006 Update of the Breast Cancer Follow-Up and Management Guidelines in the Adjuvant Setting

PURPOSE To update the 1999 American Society of Clinical Oncology (ASCO) guideline on breast cancer follow-up and management in the adjuvant setting. METHODS An ASCO Expert Panel reviewed pertinent information from the literature through March 2006. More weight was given to studies that tested a hypothesis directly relating testing to one of the primary outcomes in a randomized design. RESULTS The evidence supports regular history, physical examination, and mammography as the cornerstone of appropriate breast cancer follow-up. All patients should have a careful history and physical examination performed by a physician experienced in the surveillance of cancer patients and in breast examination. Examinations should be performed every 3 to 6 months for the first 3 years, every 6 to 12 months for years 4 and 5, and annually thereafter. For those who have undergone breast-conserving surgery, a post-treatment mammogram should be obtained 1 year after the initial mammogram and at least 6 months after completion of radiation therapy. Thereafter, unless otherwise indicated, a yearly mammographic evaluation should be performed. Patients at high risk for familial breast cancer syndromes should be referred for genetic counseling. The use of CBCs, chemistry panels, bone scans, chest radiographs, liver ultrasounds, computed tomography scans, [18F]fluorodeoxyglucose-positron emission tomography scanning, magnetic resonance imaging, or tumor markers (carcinoembryonic antigen, CA 15-3, and CA 27.29) is not recommended for routine breast cancer follow-up in an otherwise asymptomatic patient with no specific findings on clinical examination. CONCLUSION Careful history taking, physical examination, and regular mammography are recommended for appropriate detection of breast cancer recurrence.

Breast Cancer Follow-Up and Management After Primary Treatment: American Society of Clinical Oncology Clinical Practice Guideline Update

PURPOSE To provide recommendations on the follow-up and management of patients with breast cancer who have completed primary therapy with curative intent. METHODS To update the 2006 guideline of the American Society of Clinical Oncology (ASCO), a systematic review of the literature published from March 2006 through March 2012 was completed using MEDLINE and the Cochrane Collaboration Library. An Update Committee reviewed the evidence to determine whether the recommendations were in need of updating. RESULTS There were 14 new publications that met inclusion criteria: nine systematic reviews (three included meta-analyses) and five randomized controlled trials. After its review and analysis of the evidence, the Update Committee concluded that no revisions to the existing ASCO recommendations were warranted. RECOMMENDATIONS Regular history, physical examination, and mammography are recommended for breast cancer follow-up. Physical examinations should be performed every 3 to 6 months for the first 3 years, every 6 to 12 months for years 4 and 5, and annually thereafter. For women who have undergone breast-conserving surgery, a post-treatment mammogram should be obtained 1 year after the initial mammogram and at least 6 months after completion of radiation therapy. Thereafter, unless otherwise indicated, a yearly mammographic evaluation should be performed. The use of complete blood counts, chemistry panels, bone scans, chest radiographs, liver ultrasounds, pelvic ultrasounds, computed tomography scans, [(18)F]fluorodeoxyglucose-positron emission tomography scans, magnetic resonance imaging, and/or tumor markers (carcinoembryonic antigen, CA 15-3, and CA 27.29) is not recommended for routine follow-up in an otherwise asymptomatic patient with no specific findings on clinical examination.

Transdisciplinary unifying implications of circadian findings in the 1950s

A few puzzles relating to a small fraction of my endeavors in the 1950s are summarized herein, with answers to a few questions of the Editor-in-Chief, to suggest that the rules of variability in time complement the rules of genetics as a biological variability in space. I advocate to replace truisms such as a relative constancy or homeostasis, that have served bioscience very well for very long. They were never intended, however, to lower a curtain of ignorance over everyday physiology. In raising these curtains, we unveil a range of dynamics, resolvable in the data collection and as-one-goes analysis by computers built into smaller and smaller devices, for a continued self-surveillance of the normal and for an individualized detection of the abnormal. The current medical art based on spotchecks interpreted by reference to a time-unqualified normal range can become a science of time series with tests relating to the individual in inferential statistical terms. This is already doable for the case of blood pressure, but eventually should become possible for many other variables interpreted today only based on the quicksand of clinical trials on groups. These ignore individual differences and hence the individuals needs. Chronomics (mapping time structures) with the major aim of quantifying normalcy by dynamic reference values for detecting earliest risk elevation, also yields the dividend of allowing molecular biology to focus on the normal as well as on the grossly abnormal.

ACR Appropriateness Criteria® on Postmastectomy Radiotherapy. Expert Panel on Radiation Oncology-Breast

This summary focuses on the role of postoperative radiation therapy in patients treated with modified radical mastectomy for invasive breast cancer, particularly in patients receiving systemic therapy.

ACR Appropriateness Criteria (registered) on Postmastectomy Radiotherapy

This summary focuses on the role of postoperative radiation therapy in patients treated with modified radical mastectomy for invasive breast cancer, particularly in patients receiving systemic therapy.

Circadian variation in urinary melatonin in clinically healthy women in Japan and the United States of America

Urinary melatonin excretion is lower in East-Asian (Japanese) than in North-American (whites of mixed ethnic origin) women. Moreover, a statistically significant circadian rhythm is demonstrated by population-mean cosinor in the data pool from both groups of women. Furthermore, statistical significance characterizes interactions of effects from geographic differences (between ethnic groups) with temporal factors. Such spatio-temporal interactions await further scrutiny with a view inter alia of carcinogenesis as it is influenced by a spectrum of intermodulating rhythms.

American College of Radiology Appropriateness Criteria® on Conservative Surgery and Radiation: Stages I and II Breast Carcinoma

BACKGROUND During the past 2 decades, breast conservation therapy (BCT) has become firmly established as a standard therapeutic approach for eligible women with early-stage breast cancer. Breast radiation after conservative surgery is an integral component of BCT, resulting in comparable local control and equivalent survival to mastectomy. Successful breast conservation relies on understanding key elements for patient selection, evaluation, treatment contraindications, radiation therapy methods, and integration with systemic therapy. METHODS The Appropriateness Criteria Committee of the American College of Radiology convened an expert panel to examine BCT for early-stage breast cancer. By using a modified Delphi technique to generate consensus, the expert panel responded to questionnaires on 9 clinical cases that address various key elements of breast conservation. A literature review on BCT led to the generation of an evidence table to support the consensus and overview. RESULTS Consensus for appropriateness criteria for BCT was produced for various clinical scenarios commonly encountered in practice. These topics include radiation oncology management issues related to young patient age, sentinel node biopsy, elderly patients, other histology, positive margins, extensive intraductal component, node-positive breast cancer, genetic breast cancer, partial breast irradiation, and systemic therapy. Radiation methods for BCT are reviewed. CONCLUSION The Breast Cancer Panel has generated a consensus of up-to-date guidelines for the appropriate use of radiation for BCT by using a modified Delphi process for the American College of Radiology Appropriateness Criteria.

Chronobiology, Radiobiology and Steps Toward the Timing of Cancer Radiotherapy

Radiotherapists and most radiobiologists approach the organism and its responsiveness, e.g., its radiosensitivity, as a more or less constant entity. Radiotherapy is hence scheduled during ‘regular’ working hours on weekdays only, as a function of practicality. In the past few decades, however, a quantitative science, chronobiology, has developed. This science shows that the host harboring a malignancy and some malignancies themselves are dynamic entities. Human and other hosts exhibit recurrent changes. These can be assessed by inferential statistical means. Thus, a variety of bioperiodicities is uncovered. Their frequencies range from 1 cycle in less than 20 hours (ultradians), over one in about 24 hours (circadians) to one cycle in more than 28 hours (infradians). Infradians include changes with a frequency of 1 cycle in about a week (circaseptans) or in about a year (circannuals), as well as about 30-day cycles (circatrigintans). These latter cycles are found in menstrually cycling women (but also years before the first and decades after the last menstruation); furthermore, circatrigintans are also found in men (66).

Chronobiologic assessment of human blood pressure variation in health and disease

Once long and dense measurement series are available, biologic rhythm characteristics are readily computed. To assess such characteristics, we present suitable methods for blood pressure data collection and analysis. Since intra- and inter-individual differences are greater for blood pressure than for many other physiologic variables, any rhythm should and can be assessed for the individual subject by an inferential statistical approach. Circadian rhythms are thus mapped in human blood pressure in health and disease, under ordinary conditions and in social isolation, and can be shifted in their timing by changes in work schedule. Under all of the foregoing conditions, these rhythms account for a large part of the variability in blood pressure measurements. Their assessment renders changes in blood pressure predictable to a substantial degree, whereas their neglect can lead to false positive and false negative diagnoses of “hypertension”. Changes in a measure of the extent of reproducible change, such as the circadian amplitude, can lead to amplitude-hypertension occurring before the 24-h mean becomes elevated: mesor-hypertension. When changes in biologic rhythm characteristics precede an elevation of the 24-h mean of systolic blood pressure, they are harbingers of cardiovascular disease. Once automatic and/or self-measurement covers at least 48 hours with proper density, rhythmometry yields stable characteristics. High school students and adults alike can handle inferential statistical tests whereby rhythm characteristics a) are determined in actual or presumed health and b) may be found to be altered, the alteration (indicating, e.g., amplitude and/or mesorhypertension) prompting intervention. Statistical tests also gauge the effect of intervention, motivate compliance and thus contribute toward the success of preventive or curative measures. A system of education and software for rhythm analysis, wedded to hardware for self- and automatic blood pressure measurement, is particularly suitable for screening, diagnosis and the optimization by timing of non-drug and drug treatments to enhance the desired effect and to reduce side effects. Rhythmometry of data from room-restricted automatic monitoring demonstrates the effect of a shift from a betablocker to a placebo within 24 hours and corroborates it within 48 hours.

Oxygen uptake rhythms in a cockroach gauged by variance spectra

Der Sauerstoffverbrauch vonPeriplaneta americana (L.) wurde im Dauerlicht und im 24-stündigen Licht-Dunkelwechsel bei 30, 24 oder 18°C alle 20 min bestimmt. Im Varianzspektrum dieser Beobachtungsreihen lassen sich neben der ungefähren Tagesperiodik (Circadian-Periodik) auch höherfrequente, unregelmässigere und weniger prominente Rhythmen nachweisen.