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Due to the technical difficulties involved in identifying BRCA1/2 genetic mutations, the affected patients have to be investigated before testing can be made available to all the relatives at risk. Here, we studied the attendance rates at cancer genetic clinics (CGC) and the uptake of genetic testing in first/second degree relatives after the first BRCA1 mutated woman with cancer had been informed in the family. We carried out a survey on French cancer geneticists involved in breast/ovarian CGC, asking them to select their first three BRCA1 family records. Data collection was carried out retrospectively by telephone interview with a standardised closed item questionnaire. Considering only those families (n=37) where the index case had been informed for at least 8 months at the time of the survey, the overall attendance at CGC of first/second degree relatives (n=419) was 31.7% (n=133) and the overall uptake of BRCA1 testing was 26.7% (n=112). Among those who attended the CGC (n=133), 84.2% (n=112) requested genetic testing (95% confidence interval: 78–90.4%). Among the first degree relatives, the unaffected women who attended accounted for 59.8% and 51.2% requested testing after the index case had been informed. Women with cancer had a higher attendance rate (83.3%) than unaffected women (36.1%) (Odds Ratio (OR)=8.86; p<0.001) and first degree relatives (51.4%) than second degree relatives (17.9%) (OR=2.87; p<0.001); women (43%) also attended more frequently than men (16%) (OR=3.97, p<0.001). In French BRCA1 mutated families, female first degree relatives of the index patient show the most interest in genetic testing. Copyright © 2000 John Wiley & Sons, Ltd.

The paper examines two large-scale, North-American and European clinical trials designed to validate two commercially available genomic tumor signatures that predict a patient's risk of breast cancer recurrence and response to chemotherapy. The paper builds on empirical evidence from the two trials to explore the emergence of diverse regulatoryscientific hybrids, i.e. configurations of genomic practice and bioclinical work that depend on linkages between technical, commercial, patient, clinical, and legal interests and institutions. The development of the genomic signatures for each trial -Oncotype DX and MammaPrint -has followed quite different routes. Oncotype began as a commercial platform: the company that produced it did not discover a signature but rather constructed it by asking users at every step what clinical question they wanted the signature to answer and what data would be credible in that regard. The test has been designed to minimally disrupt existing clinical workflows. MammaPrint, on the other hand, began as a breast cancer signature: the researchers who discovered it, at the Netherlands Cancer Institute (NKI), established a company to commercialize it as a test after the fact. MammaPrint requires a change in pathologists' routines. Thus, while these two trials signify a new departure for clinical cancer trials on a number of levels -they both incorporate new models of interaction between biotech companies and public research, and they both aim to establish the clinical relevance of genomic markersthey also embody different socio-technical scripts: one attempts to accommodate established routines, while the other openly challenges prevailing evidential hierarchies and existing biomedical configurations.

The recent development of cancer precision medicine is associated with the emergence of ‘molecular tumour boards’ (MTBs). Attended by a heterogenous set of practitioners, MTBs link genomic platforms to clinical practices by establishing ‘actionable’ connections between drugs and molecular alterations. Their activities rely on a number of evidential resources – for example databases, clinical trial results, basic knowledge about mutations and pathways – that need to be associated with the clinical trajectory of individual patients. Experts from various domains are required to master and align diverse kinds of information. However, rather than examining MTBs as an institution interfacing different kinds of expertise embedded in individual experts, we argue that expertise is the emergent outcome of MTBs, which can be conceptualised as networks or ‘agencements’ of humans and devices. Based on the ethnographic analysis of the activities of four clinical trial MTBs (three in France and an international one) and of two French routine‐care MTBs, the paper analyses how MTBs produce therapeutic decisions, centring on the new kind of expertise they engender. The development and activities of MTBs signal a profound transformation of the evidentiary basis and processes upon which biomedical expertise and decision‐making in oncology are predicated and, in particular, the emergence of a clinic of variants.

This paper seeks to make a contribution to the discussion on what clinical work consists of in biomedicine. It draws on the comparison between two clinical practices: (1) cancer genetics of breast/ovarian and colon cancers; and (2) psychiatric genetics of autism and its related syndromes. We argue that the clinic does not reflect genetic reductionism, nor does it entail a straightforward return to the previous clinical tradition. We show that the clinic is affected by three changes in the practices that we studied. The first change concerns clinical settings: clinical work is now performed by ‘bioclinical collectives’, gathering researchers and clinicians from various disciplines and activities, and conjointly searching biology and pathology. The second change concerns the content of clinical work that we propose to call ‘clinic of mutations’. This clinic involves the intense work of collecting and comparing multiple and heterogeneous data to document the biological nature and the clinical relevance of mutations, whose status is ambiguous and whose effects are uncertain. The third change concerns the dynamics of clinical work, which is now overlapping with research. As a consequence, the elaboration of a judgment and a medical decision is no longer a matter of simply making a diagnosis or prognosis. Rather it consists in accounting for nosographic domains and descriptive and interpretive models of diseases, into which mutations may plausibly play a role. We conclude with a discussion of the form of objectivity underlying clinical work in biomedicine. Our contention is that in the current post-genomic era, thinking of genetic markers as objective proofs of a disease or a risk of disease is definitely inappropriate. Rather, the clinic has to constantly produce the meaning and relevance of mutations and biomedical entities that tend to proliferate and regularly invade the clinical settings.

Collaborative forms of work such as extended networks, expert groups, and consortia increasingly structure biomedical activities. They are particularly prominent in the cancer field, where procedures such as multicenter clinical trials have been instrumental in establishing the specialty of oncology, and subfields such as cancer genetics, where bioclinical activities—for example, testing for breast and ovarian cancer (BRCA) genes and follow-up interventions—are predicated on the articulation of a number of tasks performed by new clinical collectives. In this article, we examine the founding and development of a French bioclinical collective—the Groupe Génétique et Cancer (GGC)—that coordinates and structures the activities of most French actors in cancer genetics and operates simultaneously in the clinical, research, and regulatory domains. To examine the group’s structure and dynamics, the article combines information gathered through traditional fieldwork methods with information elicited from a coauthorship and semantic-network analysis of the publications of GGC members from 1969 to 2001.

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