A 36-item short-form (SF-36) was constructed to survey health status in the Medical Outcomes Study. The SF-36 was designed for use in clinical practice and research, health policy evaluations, and general population surveys. The SF-36 includes one multi-item scale that assesses eight health concepts: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical or emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions. The survey was constructed for self-administration by persons 14 years of age and older, and for administration by a trained interviewer in person or by telephone. The history of the development of the SF-36, the origin of specific items, and the logic underlying their selection are summarized. The content and features of the SF-36 are compared with the 20-item Medical Outcomes Study short-form.

https://www.jstor.org/stable/pdf/3765916.pdf

The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection.

Breast cancer patients with the same stage of disease can have markedly different treatment responses and overall outcome. The strongest predictors for metastases (for example, lymph node status and histological grade) fail to classify accurately breast tumours according to their clinical behaviour. Chemotherapy or hormonal therapy reduces the risk of distant metastases by approximately one-third; however, 70-80% of patients receiving this treatment would have survived without it. None of the signatures of breast cancer gene expression reported to date allow for patient-tailored therapy strategies. Here we used DNA microarray analysis on primary breast tumours of 117 young patients, and applied supervised classification to identify a gene expression signature strongly predictive of a short interval to distant metastases ('poor prognosis' signature) in patients without tumour cells in local lymph nodes at diagnosis (lymph node negative). In addition, we established a signature that identifies tumours of BRCA1 carriers. The poor prognosis signature consists of genes regulating cell cycle, invasion, metastasis and angiogenesis. This gene expression profile will outperform all currently used clinical parameters in predicting disease outcome. Our findings provide a strategy to select patients who would benefit from adjuvant therapy.

/pdf/gene-expression-profiling-predicts-clinical-outcome-of-5bu8dmnf6h.pdf

Gene expression profiling predicts clinical outcome of breast cancer

Background and Purpose—The authors present an overview of the current evidence and management recommendations for evaluation and treatment of adults with acute ischemic stroke. The intended audienc...

/pdf/guidelines-for-the-early-management-of-patients-with-acute-19udbft6e7.pdf

Guidelines for the Early Management of Patients With Acute Ischemic Stroke A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association

https://vascular.stanford.edu/content/dam/sm/vascular/documents/endovasc/guidelines/PIIS0741521406022968.pdf

Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II)

Background A more accurate means of prognostication in breast cancer will improve the selection of patients for adjuvant systemic therapy. Methods Using microarray analysis to evaluate our previously established 70-gene prognosis profile, we classified a series of 295 consecutive patients with primary breast carcinomas as having a gene-expression signature associated with either a poor prognosis or a good prognosis. All patients had stage I or II breast cancer and were younger than 53 years old; 151 had lymph-node–negative disease, and 144 had lymph-node–positive disease. We evaluated the predictive power of the prognosis profile using univariable and multivariable statistical analyses. Results Among the 295 patients, 180 had a poor-prognosis signature and 115 had a good-prognosis signature, and the mean (±SE) overall 10-year survival rates were 54.6±4.4 percent and 94.5±2.6 percent, respectively. At 10 years, the probability of remaining free of distant metastases was 50.6±4.5 percent in the group with a...

/pdf/a-gene-expression-signature-as-a-predictor-of-survival-in-1f6irz2ok6.pdf

A Gene-Expression Signature as a Predictor of Survival in Breast Cancer

Tamoxifen for breast-cancer prevention. Authors' reply

This paper outlines the necessary steps involved in setting up and administering a clinical trial. The importance of adequate preparation, with careful definition of priorities and objectives, is emphasized. Guidelines for writing a clinical protocol are discussed in detail, as well as aids to deal with the running of the study, statistical planning, and presentation of results. The principle of different types of study, methods of patient assessment, and an overall plan of study, have already been introduced in the preceding paper.

Guidelines for planning clinical trials.

1030 Background: IBIS 1 is a double-blind, randomised, placebo-controlled trial to evaluate tamoxifen (20 mg, o, daily, 5 years) in preventing breast cancer (BC) in healthy women aged 35–70 at increased risk of BC. Risk was based on family history (most) and high risk benign pathology. It was anticipated that recruitment needed to go beyond conventional medical sources. The trial was conducted by the ANZ BCTG in Australia and New Zealand. Methods: : A national Recruitment Coordinator developed strategies involving print and electronic media, medical sources (GP's, breast clinics, high-risk clinics and screening) and ‘word-of-mouth’ (BC patients, relatives). Monthly print media releases or Community Service Announcements (CSA's) on radio or TV were sent widely in Australia and New Zealand. A free call number was established for enquiries which were forwarded weekly to Study Coordinators (SC's) at 19 IBIS 1 centres. SC's responded to enquiries and determined eligibility. Results: Accrual targets were exceed...

Prevention and treatment trials need different recruitment strategies: Experience from the IBIS 1 prevention trial in Australia and New Zealand

Background: AIMSS is experienced by approximately half of women taking an aromatase inhibitor (AI), impairing quality of life and in some leading to AI discontinuation. There is a lack of evidence for effective AIMSS treatments. Aim: To investigate the importance of AIMSS in Australian women with early breast cancer. Method: A survey invitation was distributed to 2390 members of the BCNA Review and Survey Group in April 2014. The online questionnaire consisted of 45 questions covering demographics, AI use, clinical manifestations and risk factors for AIMSS, reasons for AI discontinuation and efficacy of interventions used for AIMSS. AIMSS was defined as joint pain or stiffness that developed or worsened after commencing an AI. Results: Of 594 respondents, 370 (62%) were eligible. Reasons for exclusion were: preinvasive disease, locally advanced/metastatic breast cancer, or other reason. Eligible respondents had a median age range of 50-59 years. Duration of AI use varied (26%1year, 64% 1-5years, 10% 5years). 57% had received adjuvant chemotherapy. 43% of these commenced AI within 3 months of chemotherapy and 30% within 3-6 months of chemotherapy. A vitamin D test was performed in 64% of women and 68% were currently using vitamin D supplements. Joint pain during menopause was reported by 22% of respondents. AIMSS occurred in 302/370 women (81%). Of those who developed AIMSS, sites affected were feet (68%), hands or wrists (65%), knees (62%), hips (56%), shoulders or elbows (49%), back (46%), or neck (3%). 34% of women had considered stopping an AI because of AIMSS. 99 (27%) of respondents had discontinued AI for any reason and of these 68% discontinued because of AIMSS. Non-AIMSS symptoms identified as reasons for discontinuation included fatigue, vaginal/urinary symptoms and hot flushes. In respondents who discontinued AI, 20% ceased use in the first 3 months, 30% during months 3-12 and 38%12 months. 42% of respondents who discontinued an AI restarted the same or a different AI after a treatment break. To manage AIMSS 23% of respondents used doctor prescribed medications (eg anti-inflammatories, codeine, morphine,), 55% over the counter (OTC) or complementary medicines (eg low dose anti-inflammatories, paracetamol, chondroitin, fish or krill oil, glucosamine, and vitamin D) and 29% alternative therapies (eg acupuncture, massage, Tai Chi and yoga). Respondents identified the following in each of the above categories as most successful in relieving AIMSS symptoms: doctor prescribed anti-inflammatories, paracetamol and yoga. Doctor prescribed medications and OTC/complementary medicine either completely or significantly relieved AIMSS in 12% and 25% of cases respectively. 27% of respondents found that one or more of the interventions that they had used to manage AIMSS helped prevent AI discontinuation. Conclusion: AIMSS is a significant issue for Australian women and is an important reason for AI discontinuation. Women use a number of interventions to manage AIMSS, however their efficacy appears limited. Effective AIMSS interventions are needed, to improve quality of life and reduce AI discontinuation. Citation Format: Janine M Lombard, Nicholas Zdenkowski, Kathy Wells, Nicca Grant, Linda Reaby, John F Forbes, Jacquie Chirgwin. Aromatase inhibitor induced musculoskeletal syndrome (AIMSS) in Australian women with early breast cancer: An Australia and New Zealand Breast Cancer Trials Group (ANZBCTG) survey of members of the Breast Cancer Network Australia (BCNA) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-12-05.

Abstract P1-12-05: Aromatase inhibitor induced musculoskeletal syndrome (AIMSS) in Australian women with early breast cancer: An Australia and New Zealand Breast Cancer Trials Group (ANZBCTG) survey of members of the Breast Cancer Network Australia (BCNA)

Background: As compared to invasive breast cancer (IBC), HER2 is much more frequently overexpressed in ductal carcinoma in situ (DCIS). Unlike IBC, the prognostic significance of HER2 overexpression remains to be established in DCIS and large studies to investigate its predictive role are lacking. We investigated the prognostic and predictive relevance of HER2 protein and ERBB2 mRNA expression in DCIS using material from UK/ANZ DCIS trial. Methods: Formalin-fixed paraffin embedded tissues (FFPETs) were collected from patients enrolled in the UK/ANZ DCIS trial, a randomised 2X2 factorial design trial investigating role of tamoxifen, radiotherapy or both as adjuvant treatment in DCIS. ERBB2 mRNA expression was evaluated by reverse transcription followed by PCR on customized Taqman low-density arrays. ERBB2 mRNA expression was analysed as a continuous variable and also as a binary variable using a cut-off to reproduce HER2 expression distribution similar to that observed with immunohistochemistry (IHC). HER2 protein expression was evaluated by IHC using HercepTest™ and scored as per ASCO-CAP 2013 recommendations; HER2 equivocal (IHC2+) were grouped with HER2 negative (IHC 0 or 1+) for main analyses. Additional analyses using binary ERBB2 mRNA expression as a reflex test for HER2 IHC2+ were also performed. Results: HER2 protein expression was evaluable in 713 (181 events) of 755 available samples (DCIS absent or lost during assay in 42). ERBB2 mRNA expression was evaluable in 521 (134 events) of 704 available samples (DCIS absent or insufficient RNA in 51, assay failure in 132). Both results were available in 508 cases (130 events). Increase in ERBB2 mRNA expression (median 0.62; range 0.07-36.76) was associated with increased risk of in situ ipsilateral breast event (DCIS-IBE) [Hazard ratio (HR) = 1.07; 95% Confidence Interval (95%CI) 1.04-1.10; p 2 (1d.f.) 5.51; p = 0.0189] for any recurrence. The effect of radiotherapy (RT) for reducing I-IBE was greater in HER2 positive (by ERBB2 mRNA expression) cases [HR = 0.24; 95%CI 0.07-0.83; p = 0.0237] as compared with HER2 negative cases [HR = 0.60; 95%CI 0.23-1.55; p = 0.2925]. Kaplan-Meier estimates of 10-year I-IBE rates with and without RT were 4.5% (2.5%-1.4%) and 15.8% (9.6%-25.3%) in HER2 positive DCIS; rates in HER negative DCIS were 5.2% (2.1%-2.4%) and 7.3% (4.3%-12.2%) respectively. The differential benefit of RT by HER2 status was also seen for reduction in DCIS-IBE. Conclusions: HER2 overexpression is associated with increased risk of DCIS-IBE but not of I-IBE. HER2 status is predictive of radiotherapy response with larger reductions in both I-IBE and DCIS-IBE seen in HER2 positive DCIS. Citation Format: Thorat MA, Wagner S, Jones LJ, Levey PM, Bulka K, Hoff R, Sangale Z, Flake II DD, Bundred NJ, Fentiman IS, Forbes JF, Lanchbury JS, Cuzick J. Prognostic and predictive relevance of HER2 status in ductal carcinoma in situ : Results from the UK/ANZ DCIS trial. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-02.

John F. Forbes

Papers

Tamoxifen for breast-cancer prevention. Authors' reply

Guidelines for planning clinical trials.

Prevention and treatment trials need different recruitment strategies: Experience from the IBIS 1 prevention trial in Australia and New Zealand

Abstract P1-12-05: Aromatase inhibitor induced musculoskeletal syndrome (AIMSS) in Australian women with early breast cancer: An Australia and New Zealand Breast Cancer Trials Group (ANZBCTG) survey of members of the Breast Cancer Network Australia (BCNA)

Abstract P3-07-02: Prognostic and predictive relevance of HER2 status in ductal carcinomain situ: Results from the UK/ANZ DCIS trial