Negotiating jurisdictional boundaries in response to new genetic possibilities in breast cancer care: The creation of an 'oncogenetic taskscape'.

Changes in the nature and structure of healthcare pathways have implications for healthcare professionals' jurisdictional boundaries. The introduction of treatment focused BRCA1 and 2 genetic testing (TFGT) for newly diagnosed patients with breast cancer offers a contemporary example of pathway change brought about by technological advancements in gene testing and clinical evidence, and reflects the cultural shift towards genomics. Forming part of an ethnographically informed study of patient and practitioner experiences of TFGT at a UK teaching hospital, this paper focuses on the impact of a proposal to pilot a mainstreamed TFGT pathway on healthcare professionals' negotiations of professional jurisdiction. Based upon semi-structured interviews (n = 19) with breast surgeons, medical oncologists and members of the genetics team, alongside observations of breast multidisciplinary team meetings, during the time leading up to the implementation of the pilot, we describe how clinicians responded to the anticipated changes associated with mainstreaming. Interviews suggest that mainstreaming the breast cancer pathway, and the associated jurisdictional reconfigurations, had advocates as well as detractors. Medical oncologists championed the plans, viewing this adaptation in care provision and their professional role as a logical next step. Breast surgeons, however, regarded mainstreaming as an unfeasible expansion of their workload and questioned the relevance of TFGT to their clinical practice. The genetics team, who introduced the pilot, appeared cautiously optimistic about the potential changes. Drawing on sociological understandings of the negotiation of professional jurisdictions our work contributes a timely, micro-level examination of the responses among clinicians as they worked to renegotiate professional boundaries in response to the innovative application of treatment-focused BRCA testing in cancer care - a local and dynamic process which we refer to as an 'oncogenetic taskscape in the making'.

Patients' Views of Treatment-Focused Genetic Testing (TFGT): Some Lessons for the Mainstreaming of BRCA1 and BRCA2 Testing.

This paper explores patients' views and experiences of undergoing treatment-focused BRCA1 and BRCA2 genetic testing (TFGT), either offered following triaging to clinical genetics (breast cancer) or as part of a mainstreamed care pathway in oncology (ovarian cancer). Drawing on 26 in-depth interviews with patients with breast or ovarian cancer who had undergone TFGT, this retrospective study examines patients' views of genetic testing at this point in their care pathway, focusing on issues, such as initial response to the offer of testing, motivations for undergoing testing, and views on care pathways. Patients were amenable to the incorporation of TFGT at an early stage in their cancer care irrespective of (any) prior anticipation of having a genetic test or family history. While patients were glad to have been offered TFGT as part of their care, some questioned the logic of the test's timing in relation to their cancer treatment. Crucially, patients appeared unable to disentangle the treatment role of TFGT from its preventative function for self and other family members, suggesting that some may undergo TFGT to obtain information for others rather than for self.

Predicting breast cancer risk: implications of a "weak" family history.

Published guidelines adopted in many countries recommend that women whose family history of breast cancer places them at a risk>or=1.7 times that of the age-matched general population, should be considered for inclusion in special surveillance programmes. However validation of risk assessment models has been called for as a matter of urgency. The databases of the four Scottish Familial Breast Cancer clinics and the Scottish Cancer Registry have been searched to identify breast cancers occurring among 1,125 women aged 40-56, with family histories placing them below the "moderate" level of genetic risk. The observed incidence over 6 years was compared with age-specific data for the Scottish population. Our findings confirm that when there are two affected relatives (one first degree) the relative risk (RR) exceeds 1.7 regardless of their ages at diagnosis. When only one (first degree) relative was affected at any age from 40 to 55, the RR does not reach 1.7 if that relative was a mother but exceeds it if the relative was a sister. The probable explanation is that sisters are more likely than mother/daughter pairs to share homozygosity for a risk allele. Surveillance programmes might therefore accommodate sisters of women affected before age 55. Evidence that "low penetrance" alleles contributing to breast cancer risk may be recessive should be taken into account in strategies for identifying them.

Screening for familial ovarian cancer: failure of current protocols to detect ovarian cancer at an early stage according to the international Federation of gynecology and obstetrics system.

PURPOSE: To assess the effectiveness of annual ovarian cancer screening (transvaginal ultrasound and serum CA-125 estimation) in detecting presymptomatic ovarian cancer in women at increased genetic risk. PATIENTS AND METHODS: A cohort of 1,110 women at increased risk of ovarian cancer were screened between January 1991 and March 2004; 553 were moderate-risk individuals (4% to 10% lifetime risk) and 557 were high-risk individuals (> 10% lifetime risk). Outcome measurements include the number and stage of screen-detected cancers, the number and stage of cancers not detected at screening, the number of equivocal screening results requiring recall/repetition, and the number of women undergoing surgery for benign disease. RESULTS: Thirteen epithelial ovarian malignancies (12 invasive and one borderline), developed in the cohort. Ten tumors were detected at screening: three International Federation of Gynecology and Obstetrics (FIGO) stage I (including borderline), two stage II, four stage III, and one stage IV. Of the three cancers not detected by screening, two were stage III and one was stage IV; 29 women underwent diagnostic surgery but were found not to have ovarian cancer. CONCLUSION: Annual surveillance by transvaginal ultrasound scanning and serum CA-125 measurement in women at increased familial risk of ovarian cancer is ineffective in detecting tumors at a sufficiently early stage to influence prognosis. With a positive predictive value of 17% and a sensitivity of less than 50%, the performance of ultrasound does not satisfy the WHO screening standards. In addition, the combined protocol has a particularly high false-positive rate in premenopausal women, leading to unnecessary surgical intervention.

Metal Complexes of New, Chiral N(2)O(2) Tetradentate Ligands.

N,N'-Bis(2R-hydroxy-2R-phenylethyl)-N,N'-dimethyl-1R,2R-diaminocyclohexane, H(2)L1, and N,N'-bis(2S-hydroxy-2S-methylethyl)-N,N'-dimethyl-1R,2R-diaminocyclohexane, H(2)L2, have been synthesized from readily available chiral precursors. They coordinate as neutral tetradentate ligands to Ni(II) and Cu(II) ions, from which the thiocyanates [M(H(2)L)(NCS)(2)] have been isolated and the structures of the H(2)L1 complexes determined by single-crystal X-ray techniques. In the blue complex [Ni(H(2)L1)(NCS)(2)].H(2)O.2EtOH, 1, and green [Cu(H(2)L1)(NCS)(2)]. 0.5H(2)O, 2, the neutral tetradentate ligands coordinate with the cis-alpha geometry with mutually cis N-bound thiocyanate groups, though the chiral ligands adopt a different stereochemistry in the two complexes. In 2, the absolute configuration about the Cu(II) center is Delta, with the nitrogens possessing the S stereochemistry, whereas for the Ni(II) analogue, coordination gives the Lambda isomer with the R configuration at the stereogenic nitrogens. Addition of H(2)L1 or H(2)L2 to Mn(II) in basic methanol solution results in rapid aerial oxidation. Delta-cis-alpha-[Mn(L1)(OMe)(2)].MeOH, 3, was isolated as black crystals from the reaction mixture after addition of 2 mol of NaOMe. The analogous complex with (L2)(2)(-) proved extremely hygroscopic and was not obtained in pure form. Colorless crystals of Lambda-cis-alpha-[MoO(2)(L1)], 4, were precipitated from a methanolic solution of [MoO(2)(acac)(2)] and H(2)L1. The analogous reaction with H(2)L2 gave Delta-cis-alpha-[MoO(2)(L2)], 5. Structures of 3, 4, and 5 are reported. The reactions of H(2)L1 and H(2)L2 with 1 mol equiv of [Ti(OPr(i))(4)] produced the complexes Delta-cis-alpha-[Ti(L1)(OPr(i))(2)] (white solid) and Lambda-cis-alpha-[Ti(L2)(OPr(i))(2)] (colorless oil), structural assignments for which were made possible by analysis of their (1)H NOE difference spectra. Thus the coordination of these tetradentate ligands is stereospecific, but the absolute configuration of the complexes formed (Delta or Lambda) is dependent on the metal ion involved.