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Biomedical subjects

Michael Baum

Publications and source records attributed to Michael Baum.

54 records · Page 3Linked to original sources
PubMed2002

Has tamoxifen had its day?

Tamoxifen is probably the most important drug in the history of the management of breast cancer and its development is a tribute to cross talk between laboratory scientists and clinical investigators. Its use as adjuvant therapy has led to a decrease of 20-30% in age-adjusted cause-specific mortality in the developed world and it is approved in the USA for the chemoprevention of breast cancer in high-risk women. The recent ATAC and IBIS trials have challenged the supremacy of tamoxifen. The present paper is a personal view of the implications for the future use of this drug in competition with the oral aromatase inhibitors. In the opinion of the author tamoxifen will probably remain the mainstay for adjuvant therapy of postmenopausal women with hormone-responsive disease, but maturation of the ATAC data may allow a choice in selected cases. Anastrozole looks like a competitor for the future but we may have to wait another 10 years to find out.

Anastrozole↗
PubMed2002

Effect of sex steroids and coital experience on ferrets' preference for the smell, sight and sound of conspecifics.

Previous research showed that ferrets of both sexes recognize potential opposite-sex mates on the basis of volatile body odors. We compared the ability of estrogen and androgen treatments to activate a preference in gonadectomized male and female ferrets for distal cues (volatile body odors alone or volatile odors+sight+sounds) from male versus female stimulus ferrets using an airtight Y-maze and a "stimulus proximity" or a "discrete trials" testing paradigm. Sexually naive, gonadectomized male and female ferrets that received either testosterone propionate (TP) or estradiol benzoate (EB) spent equal time in proximity to goal boxes that provided either volatile odors alone or odors+sight+sounds of male and female stimulus animals. After they received coital experience, male and female subjects (treated with either EB or TP) showed a significant preference for both types of opposite-sex stimuli. When discrete trials tests were given to these ferrets prior to receiving coital experience, EB-treated females preferred to approach odor only cues, as well as odors+sight+sounds of stimulus males, and this preference was further strengthened after coital experience. Sexually naive, TP-treated males preferred to approach volatile odor cues from stimulus females; however, these animals showed an equal preference for odors+sight+sounds of stimulus females and males. Again, after coital experience, males' preference for both sets of cues from stimulus females was significantly enhanced. Thus, in sexually naive ferrets, discrete trials, but not stimulus proximity tests, revealed a preference for distal cues (body odors with or without concurrent sight and sounds) from opposite-sex conspecifics in subjects of both sexes. Coital experience significantly enhanced these preferences for heterosexual distal cues under both testing paradigms.

Animal Communication↗
PubMed2002

The changing face of breast cancer--past, present and future perspectives.

Breast cancer used to be perceived as a stigmatized disease and rates of early diagnosis were poor because women were often reluctant to present to their physician. Once a diagnosis had been made, there was no adjuvant therapy and little in the way of palliative treatment for advanced disease. Fortunately, the situation today is much improved and although breast cancer remains the most common form of cancer in women, changing attitudes have helped to ensure improved awareness and earlier presentation of patients, leading to earlier diagnosis and better prognosis. Improved detection and treatment regimes have begun to impact on breast cancer mortality; important long-term treatment goals include the prevention of both disease recurrence and the development of advanced disease. This will necessitate improvements in systemic therapies based on the biological properties of the tumor rather than relying on early diagnosis and chemo-prevention. Significant progress has been made over the last 30 years, and the future of breast cancer treatment should be faced with optimism.

Antineoplastic Agents↗
PubMed2002

The novel technique of delivering targeted intraoperative radiotherapy (Targit) for early breast cancer.

AIM: We believe that conservative treatment of early breast cancer may not require radiotherapy that encompasses the whole breast in all patients. We have developed a novel therapeutic approach that allows targeted intraoperative radiotherapy (Targit) to be safely and accurately delivered in a standard operating theatre. We are currently recruiting for a randomized trial testing whether Targit can replace the whole 6 weeks of post-operative radiotherapy after breast conserving surgery. METHODS: This paper describes the operative technique. It employs a miniature electron-beam-driven X-ray source called INTRABEAM (PeC) that emits soft X-rays (50 kV) from within the breast. The X-rays are emitted from the tip of a 10 cm x 3.2 mm diameter probe, that is enclosed in a spherical applicator (available in 2.5-5 cm diameter sizes), which in turn is inserted in the tumour bed and intraoperative radiotherapy is delivered in about 25 min. The prescribed dose is 5 and 20 Gy at 1 cm and 0.2 cm respectively, from the tumour bed. RESULTS: The biologically effective dose is 7-53 Gy for alpha/beta=10 and 20-120 Gy for alpha/beta=1.5. The quick attenuation of the radiation reduces the damage to normal tissues and allows radiotherapy to be delivered in a standard operating theatre. Tungsten impregnated rubber sheets, cut to size, are placed on the chest wall to protect the heart/lungs and over the wound to stop stray radiation. The skin dose is monitored with thermoluminescent detectors (TLDs). After wide local excision of the tumour and good haemostasis, a spherical applicator is inserted in the tumour bed and the target breast tissues are wrapped around it with a purse-string suture. Thus, true conformation of the target around the applicator source is achieved in real time. CONCLUSION: As a tumour bed boost, this technique has the potential to reduce local recurrence by avoiding geographical misses and achieving excellent dosimetry. In patients with low risk of local recurrence, it has the potential to replace the full 6 weeks of post-operative radiotherapy with considerable implications to patients and hospitals.

Breast Neoplasms↗
PubMed2002

Management of premenopausal women with early-stage breast cancer: is there a role for ovarian suppression?

There is an overwhelming body of evidence that adjuvant ovarian ablation/suppression has a favorable impact on survival for premenopausal women with hormone-responsive early-stage breast cancer. This article reviews the randomized controlled trials that provide these data and the indirect evidence suggesting that much of the benefit seen for adjuvant chemotherapy in estrogen receptor-positive patients < 50 years of age is an indirect consequence of a chemical castration. Therefore, carefully selected women may have a choice of ovarian suppression with a gonadotropin-releasing hormone (GnRH) analogue, such as goserelin, as an alternative to chemotherapy, which would allow younger premenopausal women to retain fertility. In addition, if chemotherapy is selected and the patient does not develop permanent amenorrhoea, then additional treatment with a GnRH analogue is indicated.

Adult↗
PubMed2000

Epidemiology Versus Scare Mongering: The Case for the Humane Interpretation of Statistics and Breast Cancer.

It is essential that the epidemiological aspects of breast cancer are understood by clinicians and used humanely in counselling women to compensate for the scare mongering of the media and ill informed agents of public health policy. Examples described in this paper include breast cancer awareness campaigns, the promotion of breast cancer screening, the use of oral contraceptives, and the prescription of hormone replacement therapy. The translation of relative risks into absolute numbers will allow the proper advice necessary for women to make informed choices about risk avoidance and risk management.

Journal Article↗
PubMed1999

The price of autonomy.

The randomized controlled trial produces a clash of ethical principles with the need for informed consent (autonomy) in conflict with the principles of beneficence and justice. Informed consent is one of the major rate-limiting factors of recruitment and this delays the discovery of life-saving treatments indirectly. Whilst supporting the concept of non-exploitation we wish to challenge the prevailing dogma by asking the awkward question 'what is the price of autonomy?'. Using breast cancer as an example we have developed a decision model with explicit assumptions allowing numerical values to be fed into a mathematical equation, which calculates the cost in lives. With conservative assumptions we estimate that the price of autonomy is 2500 lives over a 10-year period in the United Kingdom alone. We issue the challenge to health policy makers and ethicists to survey public opinion to determine the value placed on autonomy in the war against cancer.

Journal Article↗
PubMed1994

Clinical trials -- a brave new partnership: a response to Mrs. Thornton.

In this commentary on the previous paper it is explained that screen-detected Duct Carcinoma In Situ is effectively a new disease of unknown natural history. It is therefore impossible that 'the doctor knows best' and it is therefore both in the patient and the public's best interests that such cases are submitted to the rigours of the randomised controlled trial. Inevitably this brings the ethical dilemma of how to explain to patients the uncertainty and how to involve them in a rational decision to take part in the randomised controlled trial. It is argued that as well as there being a collective benefit for future generations of women, that we should resolve this problem now, the individual woman is likely to benefit from being treated according to a strict protocol. Nevertheless the time of diagnosis is paradoxically not the best time for a patient to become aware of these matters and it is about time that the lay public and the opinion formers recognized their responsibility to become acquainted with the benefits and the needs of the randomised controlled trial in anticipation of the day when they themselves will be patients.

Breast Neoplasms↗
PubMedDate not supplied

A roundtable discussion of aromatase inhibitors as therapy for breast cancer.

This article summarizes the conclusions of a meeting of diverse breast cancer experts who discussed issues, controversies, and new clinical trial results relevant to the use of aromatase inhibitors for treating postmenopausal women with breast cancer. The new generation of aromatase inhibitors (anastrozole, letrozole, exemestane) have largely replaced megestrol acetate as a second-line therapy in postmenopausal women with hormone-responsive advanced breast cancer. In addition, anastrozole and letrozole have been shown to be superior to tamoxifen for first-line therapy. Finally, recent results suggest that anastrozole may be superior to tamoxifen as adjuvant therapy for early stage disease in postmenopausal women with hormone-responsive disease.

Anastrozole↗
PubMedDate not supplied

Current status of aromatase inhibitors in the management of breast cancer and critique of the NCIC MA-17 trial.

BACKGROUND: The third-generation aromatase inhibitors reduce circulating estrogen levels in postmenopausal women and are well tolerated orally for breast cancer. Their role in the management of advanced breast cancer has already been recognized. This article reviews the evidence for their role in the adjuvant treatment of early-stage disease. METHODS: Three large multicenter trials are reviewed. The ATAC trial compared anastrozole and tamoxifen or a combination of the two, for 5 years from the point of diagnosis. The NCIC trial published the results of letrozole compared with placebo after the completion of 5 years of tamoxifen. Most recently, the Intergroup Exemestane Study reported a comparison of 5 years of tamoxifen vs 2 years of tamoxifen followed by 3 years of exemestane. RESULTS: The aromatase inhibitor arm in each of these studies was associated with improved disease-free survival and good tolerability. Because of the three different settings, cross-trial comparisons of the different aromatase inhibitors are impossible, but in each case the novel therapy appears promising. CONCLUSIONS: This review is critical of the early stopping of the NCIC study and recommends more mature follow-up in each case until distant disease-free or overall survival rates can be measured and then correlated with adverse events. The late onset of osteoporotic fractures is a concern that must be addressed before tamoxifen can be abandoned in favor of the aromatase inhibitor in each of the three clinical points: at diagnosis, at midway through a course of tamoxifen, and as an extension to the conventional 5-year period of endocrine therapy.

Anastrozole↗
PubMedDate not supplied

Teaching the humanities to medical students.

The decoding of the human genome offers great promise for the understanding and treatment of chronic human diseases at the last frontier. There is a widely recognised hazard that an exaggerated emphasis on molecular reductionism may lead to the loss of the essential humanitarian instincts of young doctors. To counteract this danger it is now accepted by many leading figures of the medical establishment that the undergraduate curriculum must evolve to incorporate a variety of subjects conventionally taught in the faculty of humanities at our great universities. In this article, the case is argued that the study of 'medical humanities' will enhance the empathy, communication skills, ethical standing and, paradoxically, the scientific literacy of the next generation of young doctors. As a clinical scientist, I cannot prove these assertions with an evidence base, but offer up arguments as qualitative or hypothesis generation.

Education, Medical, Undergraduate↗