Breast Neoplasms: Canney PA

Jones AL, Barlow M, Barrett-Lee PJ, Canney PA, Gilmour IM, Robb SD, Plummer CJ, Wardley AM, Verrill MW. · Department of Oncology, Royal Free and University College London Hospitals, UK. · Br J Cancer. · Pubmed #19259090 links to  free full text

Abstract: More women are living with and surviving breast cancer, because of improvements in breast cancer care. Trastuzumab (Herceptin) has significantly improved outcomes for women with HER2-positive tumours. Concerns about the cardiac effects of trastuzumab (which fundamentally differ from the permanent myocyte loss associated with anthracyclines) led to the development of cardiac guidelines for adjuvant trials, which are used to monitor patient safety in clinical practice. Clinical experience has shown that the trial protocols are not truly applicable to the breast cancer population as a whole, and exclude some women from receiving trastuzumab, even though they might benefit from treatment without long-term adverse cardiac sequelae. Consequently, five oncologists who recruited patients to trastuzumab trials, some cardiologists with whom they work, and a cardiovascular lead general practitioner reviewed the current cardiac guidelines in the light of recent safety data and their experience with adjuvant trastuzumab. The group devised recommendations that promote proactive pharmacological management of cardiac function in trastuzumab-treated patients, and that apply to all patients who are likely to receive standard cytotoxic chemotherapy. Key recommendations include: a monitoring schedule that assesses baseline and on-treatment cardiac function and potentially reduces the overall number of assessments required; intervention strategies with cardiovascular medication to improve cardiac status before, during, and after treatment; simplified rules for starting, interrupting and discontinuing trastuzumab; and a multidisciplinary approach to breast cancer care.

Falandry C, Canney PA, Freyer G, Dirix LY. · Department of Medical Oncology, Centre Hospitalier Lyon Sud, Pierre-Bénite, France. · Ann Oncol. · Pubmed #19254941 No free full text.

Abstract: Aromatase inhibitors (AIs) are well established in the treatment of metastatic hormone-sensitive breast cancer in postmenopausal women. Cyclooxygenase (COX)-2 inhibitors have demonstrated efficacy in reducing cancer risk in animal and human studies. In several preclinical studies, combination AI plus COX-2 inhibitor therapy has shown a synergistic antitumor effect. This review describes the utility of AI plus COX-2 inhibitor therapy and discusses the completed and ongoing clinical trials investigating treatment with the AI exemestane and the COX-2 inhibitor celecoxib in the neo-adjuvant and metastatic breast cancer settings. In general, combination therapy had comparable or better efficacy compared with AI monotherapy using the end points of progression-free survival, overall response rate, clinical benefit rate, time to progression, and duration of clinical benefit. All therapies were well tolerated. There appeared to be a beneficial impact on serum lipid levels for patients receiving combination therapy in a neo-adjuvant trial despite the known cardiovascular toxicity risk associated with COX-2 inhibitors. In conclusion, AIs plus COX-2 inhibitors have shown promising efficacy and safety for the treatment of patients with metastatic breast cancer. Careful monitoring during future trials will be necessary to accurately assess the risk-benefit ratio of combination therapy.

Awada A, Albanell J, Canney PA, Dirix LY, Gil T, Cardoso F, Gascon P, Piccart MJ, Baselga J. · Medical Oncology Clinic, Institut Jules Bordet, Brussels, Belgium. · Br J Cancer. · Pubmed #18454159 links to  free full text

Abstract: The aim of this study was to determine the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of bortezomib plus docetaxel in patients with anthracycline-pretreated advanced/metastatic breast cancer. Forty-eight patients received up to eight 21-day cycles of docetaxel (60-100 mg m(-2) on day 1) plus bortezomib (1.0-1.5 mg m(-2) on days 1, 4, 8, and 11). Pharmacodynamic and pharmacokinetic analyses were performed in a subset of patients. Five patients experienced DLTs: grade 3 bone pain (n=1) and febrile neutropenia (n=4). The MTD was bortezomib 1.5 mg m(-2) plus docetaxel 75 mg m(-2). All 48 patients were assessable for safety and efficacy. The most common adverse events were diarrhoea, nausea, alopecia, asthenia, and vomiting. The most common grade 3/4 toxicities were neutropenia (44%), and febrile neutropenia and diarrhoea (each 19%). Overall patient response rate was 29%. Median time to progression was 5.4 months. In patients with confirmed response, median time to response was 1.3 months and median duration of response was 3.2 months. At the MTD, response rate was 38%. Pharmacokinetic characteristics of bortezomib/docetaxel were comparable with single-agent data. Addition of docetaxel appeared not to affect bortezomib inhibition of 20S proteasome activity. Mean alpha-1 acid glycoprotein concentrations increased from baseline at nearly all time points across different bortezomib dose levels. Bortezomib plus docetaxel is an active combination for anthracycline-pretreated advanced/metastatic breast cancer. The safety profile is manageable and consistent with the side effects of the individual agents.

Canney PA, Machin MA, Curto J. · Beatson Oncology Centre, Western Infirmary, Dumbarton Road, Glasgow G11 6NT, UK. · Eur J Cancer. · Pubmed #17027257 No free full text.

Abstract: BACKGROUND: This was a feasibility study of the combination of Exemestane and the cyclooxygenase-2 (COX-2) inhibitor Celecoxib in advanced breast cancer. PATIENTS AND METHODS: Post-menopausal women with histologically proven, hormone receptor positive, advanced breast cancer who had progressive disease, normal blood counts, liver and renal function were eligible. Exemestane was given at a dose of 25 mg daily and Celecoxib at a dose of 400 mg bd. Responses were assessed according to RECIST criteria and toxicity was accessed according to CTC. The primary end-point was the percentage of patients who had neither discontinued therapy nor progressed at 6 months ('treatment successes'). RESULTS: Fifty-three eligible patients were enrolled. Of 30 patients with target lesions, 4 (13%) had a complete response (CR), 12 (40%) a partial response (PR) and 5 (17%) stable disease (SD). The best response in 18 of the 23 patients with no target lesions at baseline was stable disease. The clinical benefit (CR, PR+SD) for the whole group was therefore 39/53 (74%). The 'treatment success' rate was 60%. There were two non-malignant deaths which may have been associated with treatment. CONCLUSION: The combination of Exemestane and Celecoxib shows promising activity and tolerability and these results support the use of this combination in phase III clinical trials of short duration treatments.

MacGregor CA, Canney PA, Patterson G, McDonald R, Paul J. · Beatson Oncology Centre, Western Infirmary, Dumbarton Road, Glasgow G11 5NT, Scotland, UK. · Eur J Cancer. · Pubmed #15763646 No free full text.

Abstract: Menopausal symptoms are a major survivorship issue for patients treated for breast cancer. There are increasing concerns over the use of hormone replacement therapy (HRT) in this setting and a growing consumer interest in "natural" therapies. It had been suggested that soy phyto-oestrogens might be beneficial in the treatment of menopausal symptoms. Seventy-two patients with a histologically confirmed pre-existing diagnosis of breast cancer who were having menopausal symptoms were randomised between 12 weeks of treatment with soy capsules or placebo. Quality of life and menopausal symptom scores were assessed at baseline, 4, 8 and 12 weeks. There was no statistical difference in menopausal symptom scores or quality of life between the two arms of the study.

Canney PA, Deehan C, Glegg M, Dickson J. · Beatson Oncology Centre, Western Infirmary, Glasgow, Scotland. · Br J Radiol. · Pubmed #10673950 links to  free full text

Abstract: Left-sided post-operative radiotherapy fields for the treatment of breast cancer inevitably encompass the heart within the treatment volume, resulting in late mortality which may negate the cause-specific survival advantage of the therapy. The effect of positioning was studied in 11 patients with left-sided tumours and five with right-sided tumours receiving routine post-operative radiotherapy to the breast or chest wall as part of primary therapy for breast cancer. Using the same arrangement of glancing fields for each patient treatment position, the optimum patient positioning resulted in a reduction in cardiac dose compared to our standard patient treatment position. On the left side the reduction in mean cardiac dose was 60% (p < 0.001) and the reduction in maximum dose was 32% (p < 0.001); on the right it was 17% and 31%, respectively. The volume of cardiac tissue irradiated was also reduced for all patients. Using this optimum treatment position, cardiac dose was investigated in a further 10 patients with left-sided tumours and our standard glancing field set-up was compared with 3-dimensional planning. A further reduction of 12% in the mean cardiac dose was achieved. 5 of 10 patients had a further small reduction of 4.6% in the maximum dose and one patient had a further reduction in maximum dose of 58%. In conclusion, sophisticated radiotherapy planning can reduce cardiac doses, but optimum patient positioning is of greater importance. The general application of such relatively simple measures could have a significant positive effect on overall survival from breast cancer.

Tho LM, McIntyre A, Rosst A, Gallagher C, Yap C, Ritchie DM, Canney PA. · Department of Clinical Oncology, Beatson Oncology Centre, Glasgow, UK. · Clin Oncol (R Coll Radiol). · Pubmed #16523814 No free full text.

Abstract: AIMS: Supraclavicular fossa (SCF) radiotherapy plays an important part in the adjuvant management of breast cancer but data on acute radiotherapy toxicity are lacking, particularly when differing patient treatment positions are used to allow computed tomography planning or to reduce cardiac doses. MATERIALS AND METHODS: We evaluated SCF and breast/chest wall acute skin toxicity in a cohort of 92 women with breast cancer, who were planned in a 'T'-grip (n = 72) or 90 degrees-grip (n = 20) position, while 'on treatment' and at 6 weeks. The modified Radiation Therapy Oncology Group (RTOG) criteria were used to score toxicity. Data on age, body mass index, smoking history, type of breast operation, prior chemotherapy, radiation dose, number of fields and field size were recorded and correlated with outcome. RESULTS: Maximum SCF reaction score was RTOG 2a, with no moist desquamation observed. SCF reactions were less severe compared with chest wall reactions and no worse than breast reactions. There was significant resolution of toxicity at 6 weeks. SCF radiotherapy in 'T'-grip patients was well tolerated and no worse than the 90 degees-grip group. Pain scores and sore throat occurrences were minimal. Univariate and multivariate analyses showed that smoking was associated with worsening SCF toxicity (odds ratio [OR] 2.92; P = 0.045) and delayed healing. Incremental SCF dose worsened toxicity (OR 3.65; P = 0.023). Smoking worsened breast but not chest wall toxicity. CONCLUSIONS: SCF radiotherapy was at least as well tolerated as breast radiotherapy and better tolerated than chest wall radiotherapy. The 'T'-grip position did not affect toxicity negatively. Smoking and radiation dose affected SCF toxicity.

Al Murri AM, Bartlett JM, Canney PA, Doughty JC, Wilson C, McMillan DC. · University Department of Surgery, Royal and Western Infirmaries, Glasgow, UK. · Br J Cancer. · Pubmed #16404432 links to  free full text

Abstract: Prediction of outcome in patients with metastatic breast cancer remains problematical. The present study evaluated the value of an inflammation-based score (Glasgow Prognostic Score, GPS) in patients with metastatic breast cancer. The GPS was constructed as follows: patients with both an elevated C-reactive protein (>10 mg l(-1)) and hypoalbuminaemia (<35 g l(-1)) were allocated a score of 2. Patients in whom only one or none of these biochemical abnormalities was present were allocated a score of 1 or 0, respectively. In total, 96 patients were studied. During follow-up 51 patients died of their cancer. On multivariate analysis of the GPS and treatment received, only the GPS (HR 2.26, 95% CI 1.45-3.52, P<0.001) remained significantly associated with cancer-specific survival. The presence of a systemic inflammatory response (the GPS) appears to be a useful indicator of poor outcome independent of treatment in patients with metastatic breast cancer.

Canney PA, Sanderson R, Deehan C, Wheldon T. · Department of Radiation Oncology, Beatson Oncology Centre, Western Infirmary, Dumbarton Road, Glasgow G11 6NT. · Br J Radiol. · Pubmed #11338104 links to  free full text

Abstract: Cardiac damage is recognized to be a potentially serious side effect of breast cancer radiotherapy, the risk of which may be reduced by the choice of appropriate radiotherapy technique. We have previously described variation in physical dose to the heart dependent upon radiotherapy technique. In this paper we report the calculated improvement in normal tissue complication probability (NTCP) (for cardiac damage) achievable by these methods. Cardiac doses were calculated from dose-volume histograms (DVHs) using a "Helax" planning system for 11 patients with left-sided tumours and 5 patients with right-sided tumours. The DVH reduction algorithm of Lyman and Wolbarst [1989] was applied to each DVH to produce a value for the NTCP. For left-sided tumours, mean NTCP with the standard technique was 7.4 +/- 5.6% (range 0.6-17%) and for the optimum technique mean NTCP was 0.3 +/- 0.6% (range 0-2%) (p < 0.003 for the difference between the two techniques): a predicted reduction in late cardiac complications of 23-fold, which is not clearly evident from viewing the DVH raw data.

Russell NS, Kunkler IH, van Tienhoven G, Canney PA, Thomas J, Bartlett J, van de Vijver MJ, Belkacemi Y, Yarnold JR, Barrett-Lee PJ. · No affiliation provided · J Clin Oncol. · Pubmed #19164209 No free full text.

This publication has no abstract.

Canney PA, McIlroy P. · No affiliation provided · Clin Oncol (R Coll Radiol). · Pubmed #15487138 No free full text.

This publication has no abstract.