Rachel Ballinger

Adjuvant chemotherapy in older women (ACTION) study - what did we learn from the pilot phase?

Background:The ACTION trial was initiated to provide evidence from a randomised trial on the effects of chemotherapy in women aged over 70 years where evidence for risk and benefit are lacking.Methods:This was a randomised, phase III clinical trial for high risk, oestrogen receptor (ER) negative/ER weakly positive early breast cancer. The trial planned to recruit 1000 women aged 70 years and older, randomised to receive 4 cycles of anthracycline chemotherapy or observation. The primary endpoint was relapse-free interval. The trial included a pilot phase to assess the acceptability and feasibility of recruitment.Results:The trial opened at 43 UK centres. Information on number of patients approached was available from 38 centres. Of the 43 eligible patients that were approached, 39 were not randomised due to patients declining entry. After 10 months only 4 patients had been randomised and after discussion with the research funder, the trial was closed and funding terminated.Conclusion:Despite widespread support at several public meetings, input from patient groups including representation on the Trial Management Group, the trial failed to recruit due to the inability to convince patients to accept randomisation. It would therefore seem that randomising the patients to receive chemotherapy vs observation is not a viable design in the current era for this patient population.

Quality of Life and Patient-reported Outcomes in the Older Breast Cancer Patient

As the world population ages, the incidence of cancer will probably also increase as it is a disease predominantly affecting older people. However, those aged 70 years or more have largely been excluded from clinical trials. This review focuses on breast cancer. Increasingly there is recognition that many older breast cancer patients are being undertreated and could and should be offered the same treatments as younger patients. Comprehensive assessment of the quality of any survival benefit from treatments is also needed to ensure that in the future older patients can make fully informed decisions about their treatment options. The aim of this overview is two-fold: first to describe methods by which to assess quality of life; and second to review the recent surgical, radiotherapy, chemotherapy and other studies that include such assessment with older breast cancer patients. Current studies are also outlined, including quality of life assessments, and recommendations are made for future research in this area.

Patients’ decision-making in a UK specialist centre with high mastectomy rates

A national audit identified one breast cancer unit as having the highest mastectomy rate in the UK: 50% compared to a national average of 14% for cancers <15mm in diameter. This anomaly needed investigation. A questionnaire was sent within 2 years of their surgery to 189 breast cancer patients probing perceived surgical choice, factors in decision-making and usefulness of information. One hundred thirty-one (69%) replied, of these 97 (74%) felt they had choice of surgery. Of these, the most important factor was minimising worry about recurrence. However, only 16% knew that recurrence rates were different between types of surgery. Sixty-one percent felt their healthcare professionals had surgical preferences for them, believed that clinical issues determined these preferences, but still knew the choice was theirs. The extent to which surgical choice is offered and patients are made aware that it is their choice, may account for the high mastectomy rate in this unit.

The Neoliberal Regulatory State, Industry Interests, and the Ideological Penetration of Scientific Knowledge: Deconstructing the Redefinition of Carcinogens in Pharmaceuticals

It is argued that neoliberal political ideology has redefined the regulatory state to have greater convergence of interests and goals with the pharmaceutical industry than previously, particularly regarding acceleration and cost reduction of drug development and regulatory review. Consequently, the pharmaceutical industry has been permitted to set the agenda about how shorter term and cheaper alternative carcinogenicity testing systems are investigated for validity. The authors contend that, with the tacit approval of the neoliberal regulatory state, the commercial interests of the pharmaceutical industry framed the process and interpretation of validating these new test systems, thereby influencing what counts as knowledge about the carcinogenic status of new pharmaceuticals. While such alternative tests were occasioned by “molecularization,” the framing of their validation was not determined by technoscientific logic or a lack of standards of validation, but by the sociopolitical goals of the controlling institutions. Indeed, a different validation process could have been conducted had the priority been to develop carcinogenicity testing in the interests of public-health protection. While the resulting validation indicated that the short-term alternative tests posed small risks to the commercial interests of pharmaceutical firms, they provided little reassurance that patients would not be exposed to greater risks than before from undetected carcinogens.

Science, politics, and health in the brave new world of pharmaceutical carcinogenic risk assessment: Technical progress or cycle of regulatory capture?

The carcinogenicity (cancer-inducing potential) of pharmaceuticals is an important risk factor for health when considering whether thousands of patients on drug trials or millions/billions of consumers in the marketplace should be exposed to a new drug. Drawing on fieldwork involving over 50 interviews and documentary research spanning 2002–2010 in Europe and the US, and on regulatory capture theory, this article investigates how the techno-regulatory standards for carcinogenicity testing of pharmaceuticals have altered since 1998. It focuses on the replacement of long-term carcinogenicity tests in rodents (especially mice) with shorter-term tests involving genetically-engineered mice (GEM). Based on evidence regarding financial/organizational control, methodological design, and interpretation of the validation and application of these new GEM tests, it is argued that regulatory agencies permitted the drug industry to shape such validation and application in ways that prioritized commercial interests over the need to protect public health. Boundary-work enabling industry scientists to define some standards of public-health policy facilitated such capture. However, as the scientific credibility of GEM tests as tools to protect public health by screening out carcinogens became inescapably problematic, a regulatory resurgence, impelled by reputational concerns, exercised more control over industry’s construction and use of the tests, The extensive problems with GEM tests as public-health protective regulatory science raises the spectre that alterations to pharmaceutical carcinogenicity-testing standards since the 1990s may have been boundary-work in which the political project of decreasing the chance that companies’ products are defined as carcinogenic has masqueraded as techno-science.

Patient attitudes towards undergoing additional breast biopsy for research

BACKGROUND Acquisition of additional breast tissue has become integral to breast oncology research. This questionnaire study examines patient willingness to undergo research-dedicated breast biopsies either at time of diagnostic biopsy (T1) or after carcinoma diagnosis has been confirmed and eligibility for a specific study established (T2), and influencing factors thereof. METHODS Prior to consultation, patients attending breast clinics were recruited to complete a questionnaire examining willingness to undergo an extra fine needle aspirate (FNA) and/or core needle biopsy (CNB) for research either at T1 or T2. Descriptions of FNA and CNB procedures were supplied to those with no prior experience. Patient perspectives towards donating surplus tissue remaining from a diagnostic procedure and/or surgery for future research were also explored. FINDINGS A total of 100 patients were recruited, 42% with prior history of breast carcinoma (BC), 22% with family history of BC (FHBC) and 65%/42% with previous experience of CNB/FNA respectively. Overall, 57% were willing to undergo additional biopsy at one or both time points. Willingness to undergo additional biopsy was greater for T1 than T2, but equivalent for CNB and FNA (willingness CNB T1, 50% vs T2, 26%, willingness FNA T1 50% vs T2 29%). A statistically significant increase in willingness to undergo CNB and/or FNA at T1 and/or T2 was seen in association with prior diagnosis of BC, FHBC, previous visit to breast clinic and prior experience of breast biopsy. 83% of patients expressed a willingness to allow surplus tissue to be stored in a biobank for future research. INTERPRETATION Where possible patients should be approached to undergo baseline research biopsies at time of diagnostic process rather than subsequently. Patients do not find FNA more acceptable than core biopsy. Prior exposure to the biopsy procedure increases willingness to undergo research-dedicated biopsies.

The slide to pragmatism : a values-based understanding of 'dangerous' personality disorders

Abstract This paper reports on a qualitative study of UK mental health practitioners’ experiences of working with the contested condition, dangerous and severe personality disorder (DSPD). Our interviews focused on the issues of treatability, risk assessment and decision-making in multi-disciplinary teams. We discuss the approach of values-based medicine (VBM) as a useful framework for interpreting the data: respondents cited both explicit values (based on occupational training) and implicit values (based on personal beliefs and subjective perceptions). There was evidence of conflicting values – within individuals, between occupational groups, and between individuals in occupational groups – which led to widespread uncertainty and caution about whether and how those with ‘dangerous’ personality disorders could be treated. These disputes were resolved by a ‘slide to pragmatism’, whereby practitioners, reluctantly acknowledging their own empowerment in the process, sought to make whichever choice was least risky for their own professional reputation, and most pragmatic, given the resources available.

Specialist breast care and research nurses' attitudes to adjuvant chemotherapy in older women with breast cancer.

PURPOSE Breast cancer largely affects older women (≥ 70 y) who have historically been excluded from clinical trials; consequently, treatment is often not evidence-based. Older women may not be offered adjuvant chemotherapy due to assumptions that they would not benefit, cannot tolerate it or do not wish to have it. Specialist breast care nurses (BCN) and research nurses (RN) play an important role influencing decisions. We report the roles, attitudes and involvement of such nurses regarding adjuvant chemotherapy in older women. METHOD A questionnaire examined 259 UK BCN and RNs views about efficacy and desirability of chemotherapy in older women, participation in decision-making in MDTs, and roles when chemotherapy was discussed with patients. RESULTS 72% of BCN and 48% of RN agreed that age should not be a factor influencing who is offered chemotherapy. BCNs indicated involvement in decision-making with older breast cancer patients, discussing chemotherapy with patients at different points following diagnosis and during treatment, and proposing chemotherapy in MDT meetings. RNs were involved to a lesser extent. 69% of all nurses had not received specific training in the area and 70% thought training would be beneficial. Nurses disagreed that older patients would not tolerate or did not want chemotherapy but 1/3 agreed or were uncertain that burdens of chemotherapy outweighed benefits. A third felt that older women had less control over treatment decisions than younger women. CONCLUSIONS This study suggests a need to develop the role of specialist nurses to facilitate treatment decision-making relating to chemotherapy in older women.