Multigene expression profile testing in breast cancer: is there a role for family physicians?

BACKGROUND: Family physicians (fps) play a role in aspects of personalized medicine in cancer, including assessment of increased risk because of family history. Little is known about the potential role of fps in supporting cancer patients who undergo tumour gene expression profile (gep) testing. METHODS: We conducted a mixed-methods study with qualitative and quantitative components. Qualitative data from focus groups and interviews with fps and cancer specialists about the role of fps in breast cancer gep testing were obtained during studies conducted within the pan-Canadian canimpact research program. We determined the number of visits by breast cancer patients to a fp between the first medical oncology visit and the start of chemotherapy, a period when patients might be considering results of gep testing. RESULTS: The fps and cancer specialists felt that ordering gep tests and explaining the results was the role of the oncologist. A new fp role was identified relating to the fp-patient relationship: supporting patients in making adjuvant therapy decisions informed by gep tests by considering the patient's comorbid conditions, social situation, and preferences. Lack of fp knowledge and resources, and challenges in fp-oncologist communication were seen as significant barriers to that role. Between 28% and 38% of patients visited a fp between the first oncology visit and the start of chemotherapy. CONCLUSIONS: Our findings suggest an emerging role for fps in supporting patients who are making adjuvant treatment decisions after receiving the results of gep testing. For success in this new role, education and point-of-care tools, together with more effective communication strategies between fps and oncologists, are needed.

Health care strategies to promote earlier presentation of symptomatic breast cancer: perspectives of women and family physicians.

BACKGROUND: Many women with symptoms suggestive of a breast cancer diagnosis delay presentation to their family physician. Although factors associated with delay have been well described, there is a paucity of data on strategies to mitigate delay. OBJECTIVES: We conducted a qualitative research project to examine factors related to delay and to identify health care system changes that might encourage earlier presentation. METHODS: Individual semi-structured interviews were conducted with women who sought care 12 weeks or more after self-detection of breast cancer symptoms and with family physicians whose practices included patients meeting that criterion. RESULTS: The women and physicians both suggested a need for clearer screening mammography guidelines for women 40-49 years of age and for better messaging concerning breast awareness. The use of additional hopeful testimonials from breast cancer survivors were suggested to help dispel the notion of cancer as a "death sentence." Educational initiatives were proposed, aimed at both increasing awareness of "non-lump" breast cancer symptoms and advising women that a previous benign diagnosis does not ensure that future symptoms are not cancer. Women wanted empathic nonjudgmental access to care. Improved methods to track compliance with screening mammography and with periodic health exams and access to a rapid diagnostic process were suggested. CONCLUSIONS: A list of "at-risk situations for delay" in diagnosis of breast cancer was developed for physicians to assist in identifying women who might delay. Health care system changes actionable both at the health policy level and in the family physician's office were identified to encourage earlier presentation of women with symptomatic breast cancer.

Women's views on chemoprevention of breast cancer: qualitative study.

OBJECTIVE: To determine, in a family practice setting, women's views on incentives for and barriers to taking chemopreventive therapy for breast cancer. DESIGN: Descriptive, qualitative study using in-depth semistructured interviews. SETTING: Women's College Family Practice Health Centre, an academic centre in Toronto, Ont. PARTICIPANTS: THREE GROUPS OF WOMEN WERE RECRUITED: women who might in future be candidates for chemoprevention, women who were then candidates for chemoprevention, and then-current participants in the Study of Tamoxifen and Raloxifene (STAR) chemoprevention trial. METHOD: Women were asked about their views on taking a pill to prevent breast cancer, their hopes and expectations regarding chemoprevention, incentives for and barriers to accepting chemopreventive therapy, and their preferred sources of information. Visual analogue scales were used to estimate perceived risk of breast cancer and personal interest in chemoprevention. Participants' Gail scores, perceptions of risk of breast cancer, perceptions of likelihood of accepting chemopreventive treatment, attitudes, views, and experiences were recorded. MAIN FINDINGS: The 27 women interviewed (median age 61 years, range 38 to 77) had a mean Gail score of 3.3 (indicating a 3.3% estimated risk of breast cancer within the next 5 years), range 1.4 to 6.8. Women were very interested in chemoprevention (62% to 67% likelihood of their taking it in the next 5 years). Perceived risk of breast cancer was not correlated with actual risk or with likelihood of taking chemopreventive therapy. To accept chemoprevention, women needed to know it would lead to an acceptable decrease in risk of breast cancer and needed more information about the medication. Incentives for acceptance included clear evidence of efficacy, prevention of cancer, altruism (contributing to an important area of research), secondary gain, and the feeling of being proactive and in control. Barriers included fear of side effects, lack of information, denial, aversion to medication, the term "chemoprevention," and the effect of the "HRT fiasco." Women's most trusted information source was their family physicians. Women overestimated their risk of breast cancer. CONCLUSION: Women were interested in chemoprevention, but required more information, preferably from their family physicians. Our data suggest that at least 4 conditions must be met for women to accept chemopreventive therapy. They must believe in its effectiveness, be proactive about their health care, believe side effects will be tolerable, and be able to overcome the fear of ingesting a pill. To make the therapy more acceptable, the term "chemoprevention" should be discontinued.

Management of palpable breast lumps. Consensus guideline for family physicians.

OBJECTIVE: To describe an approach to managing women who present with palpable breast lumps. QUALITY OF EVIDENCE: Databases were searched from 1990 to 1998 using the search terms breast lumps, breast diseases, and breast cysts. Bibliographies of the articles obtained were searched for further relevant titles. Most evidence on management of breast cysts was obtained from cohort studies. Evidence on family physicians' approach to managing breast lumps is based on a review of the 1998 Canadian consensus guidelines and a review of a 1998 consensus guideline by 12 University of Toronto surgical oncologists (U of T guidelines). MAIN MESSAGE: Family physicians can manage women presenting with breast lumps if they have skill in breast cyst aspiration. Most breast cysts can be cured in minutes, thus avoiding unwarranted anxiety and eliminating unnecessary additional investigations and referrals. Women presenting with solid lesions should be referred to a surgeon. CONCLUSIONS: Breast cyst aspiration is a simple technique family physicians can use to either cure breast lumps or define appropriate cases for referral.

Hereditary breast cancer. Risk assessment of patients with a family history of breast cancer.

OBJECTIVES: To assist family physicians in stratifying women with a family history of breast cancer as being at low, moderate, or high risk of hereditary breast cancer (HBC). To present guidelines for managing each of these risk groups. QUALITY OF EVIDENCE: A MEDLINE search was conducted from January 1976 to December 1997 using key words related to breast cancer risk factors, risk assessment, prevention, and screening. Risk stratification criteria were derived empirically and assessed using retrospective chart review. MAIN FINDINGS: Although up to 20% of women in the general population have a family history of breast cancer, less than 5% are at high risk for HBC. Certain features in a family history suggest increased risk. Women with none of these features are at low risk for HBC and should have annual clinical breast examinations and mammography at least every 2 years starting at age 50. Women with one or more features of increased risk who do not meet criteria for referral to a familial cancer clinic are at moderate risk for HBC and should begin annual mammography and clinical breast examination at age 40. Women who meet referral criteria are at high risk for HBC and should be counseled regarding referral to a familial cancer clinic for more detailed risk assessment and consideration for genetic testing. All women should be taught proper breast self-examination technique and encouraged but not pressured to practise it monthly for life. CONCLUSION: A simple algorithm can assist physicians in stratifying women into low, moderate, and high HBC risk groups. Management strategies for each group are given in this article and the two following (Heisey et al page 114 and Carroll et al page 126).

Hereditary breast cancer. Identifying and managing BRCA1 and BRCA2 carriers.

OBJECTIVES: To present a strategy for identifying candidates for consideration of BRCA1 and BRCA2 mutation testing. To discuss the implications of identifying patients as BRCA1 or BRCA2 mutation carriers, and to provide recommendations for managing them. QUALITY OF EVIDENCE: A MEDLINE search from January 1990 to May 1998 was performed using the terms genetic breast screening, BRCA1, and BRCA2. The bibliographies of articles found were searched for further relevant titles. There are no published, randomized controlled clinical trials of management strategies for known BRCA carriers. Many recommendations for management are based on expert opinion only. MAIN FINDINGS: About 5% of women with breast cancer are carriers of genetic mutations. An accurate and detailed family history is the most important tool for identifying potential BRCA1 and BRCA2 mutation carriers. Women identified as carriers have a substantially increased risk of breast and ovarian cancer. Male carriers have a moderately increased risk of prostate cancer. Management strategies for carriers are not well studied but include increased surveillance, preventive surgery, chemoprevention, and lifestyle modification. CONCLUSION: Family physicians must be able to identify people at risk, to discuss management strategies, and when appropriate, to offer referral for consideration of genetic testing. There is an urgent need for research to determine the effectiveness of surveillance strategies, preventive surgery, chemoprevention, and lifestyle modification for BRCA1 and BRCA2 mutation carriers.

Hereditary breast cancer. Psychosocial issues and family physicians' role.

OBJECTIVES: To outline the psychosocial issues in hereditary breast cancer (HBC) assessment and discuss the role of family physicians. QUALITY OF EVIDENCE: A literature search using MEDLINE, CINAHL, CancerLit, and HealthStar databases was conducted from January 1990 to April 1998, using the key words breast cancer or neoplasm and familial or hereditary, genetic testing or screening, primary care or family physician or counseling, genetic counseling, psychosocial or psychological. We found only a few studies focusing on a small number of well-studied "research families." MAIN FINDINGS: Women with a family history of breast cancer were likely to be highly interested in genetic testing for cancer risk. The benefit of testing for those with negative results is reassurance. Those found to be carriers of genetic mutations might benefit from increased surveillance and prophylactic therapy. Risks of testing include anxiety, depression, guilt, altered self-image, and insurance and employment discrimination. A family physician's role is to assess risk, to provide information and support so women can make informed choices about referral to familial cancer clinics, to offer cancer surveillance, and to provide support once genetic test results are available. CONCLUSION: Genetic testing is rapidly moving from research to clinical applications. Family physicians play an integral role in educating and managing women at risk for HBC. Physicians must prepare themselves with knowledge and counseling skills to meet the challenges of this new technology.

Isolation of microorganisms able to metabolize purified natural rubber.

Bacteria able to grow on purified natural rubber in the absence of other organic carbon sources were isolated from soil. Ten isolates reduced the weight of vulcanized rubber from latex gloves by >10% in 6 weeks. Scanning electron microscopy clearly revealed the ability of the microorganisms to colonize, penetrate, and dramatically alter the physical structure of the rubber. The rubber-metabolizing bacteria were identified on the basis of fatty acid profiles and cell wall characteristics. Seven isolates were strains of Streptomyces, two were strains of Amycolatopsis, and one was a strain of Nocardia.

Parietal bone mobility in the anesthetized cat.

To quantify parietal bone motion in reference to the medial sagittal suture, a newly developed instrument was attached to the surgically exposed skull of anesthetized adult cats. The instrument differentiated between lateral and rotational parietal bone movements around the fulcrum of the suture. Bone movement was produced by external forces applied to the skull and by changes in intracranial pressure associated with induced hypercapnia, intravenous injections of norepinephrine, and controlled injections of artificial cerebrospinal fluid into the lateral cerebral ventricle. Responses varied considerably among test animals. Generally, lateral head compression caused sagittal suture closure, small inward rotation of the parietal bones, increased intraventricular pressure, transient apnea, and unstable systemic arterial blood pressure. Graded increases in intracranial volume produced stepped increases in pressure, lateral expansion at the sagittal suture, and outward rotation of the parietal bones. We attribute variations in animal response largely to differences in intracranial and suture compliance among them. Cranial suture compliance may be an important factor in defining total cranial compliance.

Evidence for allelopathy by tree-of-heaven (Ailanthus altissima).

Ailanthus altissima (Mill.) Swingle contains one or more phytotoxic compounds in roots and leaves. Activity is higher in roots, where it occurs primarily in the bark. Powdered root bark and leaflets strongly inhibited growth of garden cress (Lepidium sativum L.) when mixed with soil in Petri dishes (ID50 values=0.03 g root bark, 0.6 g leaflet/dish). The toxic material was readily extracted by methanol but not dichloromethane. Pieces of root bark mixed with soil at 2, 1, and 0.5 g/pot reduced cress biomass in the greenhouse, whereas methanol-extracted root bark did not. The inhibitory effect ofAilanthus tissues in soil was short-lived (≤4 weeks in pots in greenhouse, ≤3 days in Petri dishes in laboratory). Inhibition by root bark was sometimes superseded by stimulation. FreshAilanthus root segments placed in or on soil reduced growth of nearby cress seedlings. Fine roots were more inhibitory than coarse, and inhibition became more pronounced with increased time of soil exposure to roots. Soil collected nearAilanthus roots in the field supported reduced radicle growth of cress compared to control soil. In contrast, stemflow fromAilanthus trees stimulated cress growth. The results suggest allelopathy caused by toxin exudation from roots may contribute to the aggressiveness and persistence ofAilanthus in certain habitats.

Herbicidal effects of geldanamycin and nigericin, antibiotics from Streptomyces hygroscopicus.

Geldanamycin (2) and nigericin (1) (primarily the Na+ salt) are responsible for the phytotoxicity of a Streptomyces hygroscopicus strain found to be highly active in our screens for producers of herbicidal antibiotics. After extraction from the cells, the compounds were purified with column and thin layer layer chromatography on silica gel, bioassayed for inhibition of garden cress (Lepidium sativum L.) radicle elongation, and identified with ms, ir, nmr, and co-chromatography with authentic standards. Both caused 50% reduction in garden cress radicle growth at concentrations of 1-2 ppm and nearly complete inhibitions at 3-4 ppm. Symptoms of toxicity differed markedly for the two compounds. Geldanamycin at high concentrations caused radicles to turn brown and disintegrate, whereas, nigericin did not cause visible necrosis. Geldanamycin is structurally similar to the herbimycins, which are also produced by S. hygroscopicus and have been reported to have herbicidal activity. The phytotoxicity of geldanamycin and nigericin has stimulated investigation of their potential for use as natural product herbicides.