Observation versus late reintroduction of letrozole as adjuvant endocrine therapy for hormone receptor-positive breast cancer (ANZ0501 LATER): an open-label randomised, controlled trial.

BACKGROUND: Despite the effectiveness of adjuvant endocrine therapy in preventing breast cancer recurrence, breast cancer events continue at a high rate for at least 10 years after completion of therapy. PATIENTS AND METHODS: This randomised open label phase III trial recruited postmenopausal women from 29 Australian and New Zealand sites, with hormone receptor-positive early breast cancer, who had completed ≥4 years of endocrine therapy [aromatase inhibitor (AI), tamoxifen, ovarian suppression, or sequential combination] ≥1 year prior, to oral letrozole 2.5 mg daily for 5 years, or observation. Treatment allocation was by central computerised randomisation, stratified by institution, axillary node status and prior endocrine therapy. The primary outcome was invasive breast cancer events (new invasive primary, local, regional or distant recurrence, or contralateral breast cancer), analysed by intention to treat. The secondary outcomes were disease-free survival (DFS), overall survival, and safety. RESULTS: Between 16 May 2007 and 14 March 2012, 181 patients were randomised to letrozole and 179 to observation (median age 64.3 years). Endocrine therapy was completed at a median of 2.6 years before randomisation, and 47.5% had tumours of >2 cm and/or node positive. At 3.9 years median follow-up (interquartile range 3.1-4.8), 2 patients assigned letrozole (1.1%) and 17 patients assigned observation (9.5%) had experienced an invasive breast cancer event (difference 8.4%, 95% confidence interval 3.8% to 13.0%, log-rank test P = 0.0004). Twenty-four patients (13.4%) in the observation and 14 (7.7%) in the letrozole arm experienced a DFS event (log-rank P = 0.067). Adverse events linked to oestrogen depletion, but not serious adverse events, were more common with letrozole. CONCLUSION: These results should be considered exploratory, but lend weight to emerging data supporting longer duration endocrine therapy for hormone receptor-positive breast cancer, and offer insight into reintroduction of AI therapy. CLINICAL TRIALS NUMBER: Australian New Zealand Clinical Trials Registry (www.anzctr.org.au), ACTRN12607000137493.

Improving decision making about clinical trial participation - a randomised controlled trial of a decision aid for women considering participation in the IBIS-II breast cancer prevention trial.

BACKGROUND: Decision aids may improve informed consent in clinical trial recruitment, but have not been evaluated in this context. This study investigated whether decision aids (DAs) can reduce decisional difficulties among women considering participation in the International Breast Cancer Intervention Study-II (IBIS-II) trial. METHODS: The IBIS-II trial investigated breast cancer prevention with anastrazole in two cohorts: women with increased risk (Prevention), and women treated for ductal carcinoma in situ (DCIS). Australia, New Zealand and United Kingdom participants were randomised to receive a DA (DA group) or standard trial consent materials (control group). Questionnaires were completed after deciding about participation in IBIS-II (post decision) and 3 months later (follow-up). RESULTS: Data from 112 Prevention and 34 DCIS participants were analysed post decision (73 DA; 73 control); 95 Prevention and 24 DCIS participants were analysed at follow-up (58 DA; 61 control). There was no effect on the primary outcome of decisional conflict. The DCIS-DA group had higher knowledge post decision, and the Prevention-DA group had lower decisional regret at follow-up. CONCLUSIONS: This was the first study to evaluate a DA in the clinical trial setting. The results suggest DAs can potentially increase knowledge and reduce decisional regret about clinical trial participation.

Neoadjuvant chemotherapy with sequential anthracycline-docetaxel with gemcitabine for large operable or locally advanced breast cancer: ANZ 0502 (NeoGem).

BACKGROUND: Neoadjuvant chemotherapy has a sound rationale for use in women with large operable breast cancer, and achievement of pathological complete response (pCR) is prognostic. Epirubicin and cyclophosphamide followed by docetaxel is a standard chemotherapy regimen for early breast cancer. In metastatic breast cancer the combination of gemcitabine and a taxane has shown promising results. This phase II study investigated the efficacy and safety of incorporating gemcitabine into neoadjuvant therapy. METHODS: Female patients with operable breast cancer that was clinically T2 (≥3 cm) or T3-4, N0-1, M0 were enrolled to receive 24 weeks of neoadjuvant chemotherapy using epirubicin and cyclophosphamide followed by docetaxel and gemcitabine, plus trastuzumab if HER2-positive. The primary endpoint was the pathological complete response (pCR) rate in the breast in separate HER2-negative and HER2-positive cohorts. Secondary endpoints included pCR in both the breast and axillary lymph nodes, clinical and radiological response rates, disease free survival and safety. RESULTS: 81 patients were enrolled: 63 HER2-negative and 18 HER2-positive. 67 (84%) completed all cycles of chemotherapy, and 78 (96%) proceeded to surgery. pCR was achieved by 12 (20%) patients with HER2-negative, and 9 (53%) with HER2-positive disease. At the first interim analysis, addition of prophylactic G-CSF was recommended due to excess neutropenia. The HER2-negative cohort was closed to accrual because it did not meet the pre-specified target for pCR, and the HER2-positive cohort was closed due to slow accrual. At a median follow-up of 24 months, 12 of 81 (15%) patients had experienced a relapse of their breast cancer. CONCLUSION: Neoadjuvant gemcitabine, when added to docetaxel, after epirubicin and cyclophosphamide, did not reach the pre-specified expectations for pCR rate in HER2-negative tumours. Excess neutropenia was observed, requiring growth factor support. Addition of gemcitabine to docetaxel in this schedule cannot be recommended. Australia and New Zealand Clinical Trials Registry (www.anzctr.org.au) registration number ACTRN12606000191594.

Improving informed consent: pilot of a decision aid for women invited to participate in a breast cancer prevention trial (IBIS-II DCIS).

BACKGROUND: Patients and clinicians report difficulties with the process of informed consent to clinical trials and audiotape audits show that critical information is often omitted or poorly presented. Decision aids (DAs) may assist in improving consent. AIMS: This study piloted a DA booklet for a high priority breast cancer prevention trial, IBIS-II DCIS, which compares the efficacy of an aromatase inhibitor (anastrozole) with tamoxifen in women who have had surgery for ductal carcinoma in situ (DCIS). METHOD: Thirty-one Australian women participating in the IBIS-I breast cancer prevention trial and who are currently in follow-up agreed to read the IBIS-II DCIS participant information sheet and the DCIS DA booklet, complete a set of standardized questionnaires, and provide feedback on the DA via a semi-structured phone interview. RESULTS: Women found the DA helpful in deciding about trial participation, reporting that it aided their understanding over and above the approved IBIS-II DCIS participant information sheet and was not anxiety provoking. Women's understanding of the rationale and methods of clinical trials and the IBIS-II DCIS trial was very good; with more than 80% of items answered correctly. The only areas that were not understood well were the concepts of randomization and blinding. CONCLUSIONS: This study suggests that the DA will be acceptable to and valued by potential participants in the IBIS-II DCIS study. The revised DA is currently being evaluated prospectively in a randomized controlled trial. If successful, such DAs could transform the consent process to large clinical trials and may also reduce dropout rates.

Efficacy and safety of prone positioning for patients with acute respiratory distress syndrome.

This article presents an overview of a literature review on how prone positioning can alleviate pathophysiological changes in ARDS and improve ventilation and perfusion. Improvement of gas exchange, efficiency of oxygenation and lung function are emphasized. Literature on the pathophysiology of ARDS, and the physiological effects of prone positioning on haemodynamics and lung function is examined. There are both advantages and disadvantages in turning a patient from the supine to the prone position. There are also contraindications in rotating between the supine and prone positions. Nevertheless, by rotating patients with ARDS, it is possible to achieve a significant improvement in A-aDO2, decrease shunting, and therefore improve oxygenation without use of expensive, invasive and experimental procedures. Placing patients with ARDS in the prone position can reduce inspiratory oxygen concentrations and peak inspiratory pressures, which minimizes the chance for barotrauma and the iatrogenic effects of hyperventilation oxygen toxicity.

Breast restoration decision making.

Women diagnosed with breast cancer have many physiological and psychological adjustments to make following mastectomy. The present study described in this article sought to determine the decision-making patterns used by two groups of women. Nurses need to be well informed and professionally confident to provide the individualized care and support deserved by women throughout the breast cancer trajectory. A major outcome of such professional care is confident women who understand their disease, treatments, and methods to manage stresses as they occur.

Breast restoration decision making: enhancing the process.

The purpose of this study was to explore the breast restoration decision-making patterns used by women who opted to have their breast cancer treated by mastectomy. Sixty-four women wearing external breast prostheses and 31 women with breast reconstructions were interviewed. Modified versions of Simon's notion of "bounded rationality" and Janis and Mann's conflict model provided the conceptual scaffolding for the study. Five breast restoration decision-making patterns emerged from the analysis of the interview data: (a) Enlightened (actively seeks information, considers positive and negative aspects, and demonstrates deliberation on the alternatives), (b) Contented (passively accepts minimum information on alternatives because of a preference toward a particular type), (c) Sideliner (uncritically adopts any alternative that is easy and simple to implement), (d) Shifter (gives over the decision to others), and (e) Panic-stricken (can make no rational decision on alternatives). In the prosthesis group, the major pattern used was the Sideliner, and in the reconstruction group it was the Contented. None of the participants used the Enlightened pattern. The data indicated that there was no evidence of active information-seeking behavior or deliberation on the alternatives as part of the women's decision-making process. The findings suggest a need for a registered nurse oncology specialist to be accessible to women during the period when decisions regarding breast restoration are made. This professional has the knowledge to interact effectively with these women and serve as their advocate during the decision-making process. Implications for professional practice and a model for competent breast restoration decision making are presented.

Reasons why women who have mastectomy decide to have or not to have breast reconstruction.

Breast reconstruction after mastectomy is chosen by approximately 10 percent of Australian women. Younger women are more likely to have this surgical procedure. This suggests that there may be many factors determining this choice. Sixty-four women who wore an external postmastectomy breast prosthesis and 31 women who had postmastectomy breast reconstruction participated in the present study. The purpose was to gain a greater understanding through semi-structured interviews of why women who had breast reconstruction chose this alternative and why women who wore the external postmastectomy breast prosthesis elected not to have reconstruction. The study also ascertained how difficult it was for the women in both groups to decide their particular breast restoration alternative. The most frequently endorsed reasons for not having breast reconstruction in the prosthesis group included: (1) not essential for physical well being, (2) not essential for emotional well being, (3) not having enough information about the procedure, and (4) not wanting anything unnatural in the body. When each member of the group was asked to identify a major reason for not having reconstruction, two predominant issues emerged: (1) fearing complications and (2) perceiving themselves as being too old for the procedure. Twelve percent of the prosthesis group experienced difficulty in making the decision not to have reconstruction. Three factors accounted for this difficulty: (1) the lack of family support, (2) the inability to have a specific type of reconstruction, and (3) the perception that friends and acquaintances saw the surgery as cosmetic. The most frequently reported reasons given by the reconstruction group for having reconstruction included: (1) to get rid of the external breast prosthesis, (2) to be able to wear many different types of clothing, (3) to regain femininity, and (4) to feel whole again. The least influential factors were to improve marital and sexual relations. The major reason cited most often by this group was to feel whole again. None of the women in the reconstruction group experienced any difficulty when deciding their method of breast restoration. What factors are taken into consideration by women when they decide either to have or not to have reconstruction need to be understood by physicians. This knowledge will assist them in conveying appropriate information regarding alternatives and will help them deal with the women's concerns and/or misconceptions.

The quality and coping patterns of women's decision-making regarding breast cancer surgery.

This study addressed issues regarding the decision-making process used by women who had mastectomy as their surgical treatment for breast cancer. The seven criteria for quality decision-making and the conflict model proposed by Janis and Mann (1977) were used as the study's conceptual framework along with the notion by Simon (1957) of 'bounded rationality'. Four coping patterns emerged: vigilance (actively searches for information and advice), satisficing (being satisfied, chooses first solution that meets the desired objectives), complacency (accepts advice without questions or fully comprehending), and defensive avoidance (rationalises and avoids discussion and consideration of the problem). The participants primarily left the decision for surgical treatment of breast cancer to their surgeons using satisficing, complacency and defensive avoidance. When the option of lumpectomy was offered to some of the participants (34%), they rejected this treatment alternative using the coping patterns of satisfying and defensive avoidance. Those women who were not offered lumpectomy (66%) did not seek a rationale for not being given this alternative. The findings indicated that the women's decision-making process was halted in Stage 2 of the criteria for quality decision-making actively searched for and viewed a number of alternatives. The study's findings are discussed in relation to improving the quality of the decision-making process for women regarding their breast cancer surgical treatment.

Postmastectomy attitudes in women who wear external breast prostheses compared to those who have undergone breast reconstructions.

Sixty-four women who postmastectomy wore an external breast prosthesis and 31 women who had breast reconstruction participated in the present study. It was hypothesized that the breast prosthesis group would exhibit more negative attitudes towards their mastectomy experience compared to the breast reconstruction group. Using the Mastectomy Attitude Scale (MAS) the results indicated that both groups were satisfied with their bodies, had a positive outlook towards their lives, implied that sexuality entailed more than having breasts, and felt that mastectomy treatment was necessary to save their lives. Neither group concealed that they had a mastectomy, however, they were not prone to discuss their mastectomy experiences. The findings from the study indicate that the women postmastectomy already had or developed positive attitudes towards themselves and life in general and the method chosen for breast restoration had no apparent impact on these attitudes. Reasons for the sample's positive attitudes are discussed.

Body image, self-concept, and self-esteem in women who had a mastectomy and either wore an external breast prosthesis or had breast reconstruction and women who had not experienced mastectomy.

The perceptions of three groups of women regarding their body image, self-concept, total self-image, and self-esteem were compared. The groups included 64 women who had mastectomies and wore external breast prostheses, 31 women who had mastectomies and underwent breast reconstruction, and a control group of 78 women who had not experienced mastectomy. The body image, total self-image, and self-esteem mean scores indicated that the prosthesis and reconstruction groups had more positive feelings regarding their bodies than did the control group. There were no significant differences in self-concept among the three groups. These findings challenge a common assumption that mastectomy automatically results in psychiatric morbidity caused by an altered body image and suggest that health professionals should not make assumptions about how a woman will psychologically respond to mastectomy.

Use of physical assessment skills by Australian nurses.

The use of physical assessment skills, though limited, has been an integral part of nursing since the time of Florence Nightingale, when aids such as sight and touch were relied upon to assess patients. Now with more nurses involved in primary health the use of a wider range of physical assessment has become necessary. Below is a report of how Australian nurses are putting more of these skills into practice.

The effectiveness of an education program to teach Australian nurses comprehensive physical assessment skills.

This study investigates the effectiveness of an educational program to teach 22 registered nurses comprehensive physical assessment skills. Administration of questionnaires and tests provided measures of the nurses: a) use of physical assessment skills; b) knowledge of physical assessment; c) changes in nursing practice since learning the skills; d) barriers to the use of these learned skills. The major post program findings regarding increases in the nurses' knowledge and use of physical assessment skills, positive changes in their nursing practice and lack of barriers to their use of these skills indicates that the participants did benefit from this educational experience.

Continuing education in physical assessment: a pilot study.

This study examines the effectiveness of a five day educational program designed to teach registered nurses (RNs) comprehensive physical assessment techniques and associated skills. Tests and questionnaires measured nurses' knowledge and use of physical assessment skills before and three months after its completion. It was found that the group had increased its physical assessment knowledge and the majority were using the learned skills.