Piloting a regional collaborative in cancer surgery using a “community of practice” model

Background

Patients requiring assessment for cancer surgery encounter a complex series of steps in their cancer journey. Further complicating the process is the fact that care is often delivered in a fragmented, silo-based system. Isolated strategies to improve cancer outcomes within those systems have had inconsistent results.

Methods

A regional quality improvement collaborative was developed based on a community of practice (cop) platform, a hub-and-spoke infrastructure, and a regional steering committee linking cop improvement projects with affiliated hospitals and their strategic priorities. The cop provided an avenue for multidisciplinary teams to collect and compare their performance data and to institute regional standards through literature review, discussion, and consensus. Regional interdisciplinary teams developed a set of quality indicators linked to mutually agreed-upon care standards. A limited regional database supported feedback about performance against both provincial and regional standards.

Results

The cop approach helped to develop a multihospital collaboration that facilitated care quality improvements on a regional scale, with clinical outcomes of the improvements able to be measured. The 9 participating hospitals delivered cancer surgery in the specific disease sites according to practitioner-developed and provincially- or regionally-generated care standards and clinical pathways. Compliance with provincial evidence-based clinical guidelines improved (20% increase in 2010–2011 compared with 2006–2007). Other significant improvements included standardization and implementation of regional perioperative pathways in breast, colorectal, and prostate cancer disease sites; rectal cancer surgery centralization; increased use of sentinel lymph node biopsies in breast cancer surgery; and decreased positive surgical margin rates in prostate cancer.

Conclusions

Improved quality is likely a result of diverse confounding factors. The deliberately cultivated multihospital multidisciplinary cops have contributed to positive structural and functional change in cancer surgery in the region. This regional cop model has the potential to play an important role in the development of successful collaborations in care quality improvement.     

Canadian initiatives for locally advanced breast cancer research and treatment: inaugural meeting of the Canadian Consortium for LABC

The inaugural Canadian Consortium for LABC (locally advanced breast cancer) conference was held at Langdon Hall, Cambridge, Ontario, April 11–12, 2010. The meeting focused on current and future directions in labc treatment and research, the specific benefits of labc as a model for clinical and translational research, strategies for increased national and international collaboration, and ongoing clinical trials. Exciting Canadian initiatives in labc research are underway, focusing on identifying molecular signatures that will allow for the development of new tailored therapies. The challenge of identifying patient subgroups for accrual is being addressed through strategies to foster and improve national collaboration. This meeting report includes highlights from each presentation at the conference.     

Cost effectiveness of tac versus fac in adjuvant treatment of node-positive breast cancer

Background

This economic analysis aimed to determine, from the perspective of a Canadian provincial government payer, the cost-effectiveness of docetaxel (Taxotere: Sanofi–Aventis, Laval, QC) in combination with doxorubicin and cyclophosphamide (tac) compared with 5-fluorouracil, doxorubicin, and cyclophosphamide (fac) following primary surgery for breast cancer in women with operable, axillary lymph node–positive breast cancer.

Methods

A Markov model looking at two time phases—5-year treatment and long-term follow-up—was constructed. Clinical events included clinical response (based on disease-free survival and overall survival) and rates of febrile neutropenia, stomatitis, diarrhea, and infections. Health states were “no recurrence,” “locoregional recurrence,” “distant recurrence,” and “death.” Costs were based on published sources and are presented in 2006 Canadian dollars. Model inputs included chemotherapy drug acquisition costs, chemotherapy administration costs, relapse and follow-up costs, costs for management of adverse events, and costs for granulocyte colony-stimulating factor (g-csf) prophylaxis. A 5% discount rate was applied to costs and outcomes alike. Health utilities were obtained from published sources.

Results

For tac as compared with fac, the incremental cost was $6921 per life-year (ly) gained and $6,848 per quality-adjusted life-year (qaly) gained. The model was robust to changes in input variables (for example, febrile neutropenia rate, utility). When g-csf and antibiotics were given prophylactically before every cycle, the incremental ratios increased to $13,183 and $13,044 respectively.

Conclusions

Compared with fac, tac offered improved response at a higher cost. The cost-effectiveness ratios were low, indicating good economic value in the adjuvant setting of node-positive breast cancer patients.     

Concurrent chemoradiotherapy for locally advanced breast cancer—time for a new paradigm?

Background

In cases of locally advanced breast cancer (labc), preoperative (“neoadjuvant”) therapy was traditionally reserved to render the patient operable. More recently, neoadjuvant therapy, particularly chemotherapy, is being used in patients with operable disease to increase the opportunity for breast conservation. Despite the increasing use of preoperative chemotherapy, rates of pathologic complete response, a surrogate marker for disease-free survival, remain modest in patients with locally advanced disease and particularly so when the tumour is estrogen or progesterone receptor–positive and her2-negative. A new paradigm for labc patients is needed. In other solid tumours (for example, rectal, esophageal, and lung cancers), concurrent chemoradiotherapy (ccrt) is routinely used in neoadjuvant and adjuvant treatment protocols alike.

Results

The literature suggests that ccrt in labc patients with inoperable disease is associated with response rates higher than would be anticipated with systemic therapy alone.

Conclusions

Ongoing trials in this field are eagerly awaited to determine if ccrt should become the new paradigm.     

Breast cancer survivorship and South Asian women: understanding about the follow-up care plan and perspectives and preferences for information post treatment

Background and Objectives

As more treatment options become available and supportive care improves, a larger number of people will survive after treatment for breast cancer. In the present study, we explored the experiences and concerns of female South Asian (sa) breast cancer survivors (bcss) from various age groups after treatment to determine their understanding of follow-up care and to better understand their preferences for a survivorship care plan (scp).

Methods

Patients were identified by name recognition from BC Cancer Agency records for sa patients who were 3–60 months post treatment, had no evidence of recurrence, and had been discharged from the cancer centre to follow-up. Three focus groups and eleven face-to-face semistructured interviews were audio-recorded, transcribed verbatim, cross-checked for accuracy, and analyzed using thematic and content analysis. Participants were asked about their survivorship experiences and their preferences for the content and format of a scp.

Results

Fatigue, cognitive changes, fear of recurrence, and depression were the most universal effects after treatment. “Quiet acceptance” was the major theme unique to sa women, with a unique cross-influence between faith and acceptance. Emphasis on a generalized scp with individualized content echoed the wide variation in breast cancer impacts for sa women. Younger women preferred information on depression and peer support.

Conclusions

For sa bcss, many of the psychological and physical impacts of breast cancer diagnosis and treatment may be experienced in common with bcss of other ethnic backgrounds, but the present study also suggests the presence of unique cultural nuances such as spiritual and language-specific support resource needs. The results provide direction for designing key content and format of scps, and information about elements of care that can be customized to individual patient needs.     

A Canadian economic analysis of U.S. Oncology Adjuvant Trial 9735

Objectives

Recent results of the U.S. Oncology Adjuvant Trial 9735 demonstrated significant disease-free survival and overall survival benefits for docetaxel and cyclophosphamide (tc) compared with doxorubicin and cyclophosphamide (ac) in the adjuvant treatment of operable invasive breast cancer. Based on clinical data from the 9735 study, we evaluated the lifetime cost-effectiveness of tc compared with ac from the perspective of the Canadian publicly funded health care system.

Methods

A Markov model was developed to estimate the incremental cost per quality-adjusted life-year gained and per life-year gained. Monthly survival and risk of disease recurrence up to 7 years were obtained directly from the overall survival and disease-free survival curves in the 9735 study; life-years beyond 7 years were estimated using the average life expectancy of age-matched women in the general Canadian population. Canadian-specific resource utilization and unit costs (in 2008 Canadian dollars) were applied to estimate costs for chemotherapy administration, chemotherapy-related toxicities, recurrence, and adverse events. Health-utility scores and decrements used in the calculation of quality-adjusted life-years were derived from the literature.

Results

The lifetime cost per quality-adjusted life-year gained was $8,251 for tc compared with ac, and the cost per life-year gained was $6,842. The results were robust across a range of sensitivity analyses.

Conclusions

Cost-effectiveness, combined with efficacy and an acceptable safety profile, support the adoption of tc as an alternative to ac in Canadian clinical practice for the adjuvant treatment of operable early breast cancer.     

The role of neoadjuvant her2-targeted therapies in her2-overexpressing breast cancers

Women receiving neoadjuvant systemic therapy for primary operable or inoperable breast cancer can potentially benefit in a number of ways, but the main advantage, which has been consistently demonstrated, is improved tumour resectability. Given the improvement in outcomes with the adjuvant use of trastuzumab in patients with early-stage breast cancer positive for the human epidermal growth factor receptor 2 (her2), questions have been raised about the use of trastuzumab in the neoadjuvant setting. The present paper reviews the currently available data and outlines suggestions from a panel of Canadian oncologists about the use of trastuzumab and other her2-targeted agents in the neoadjuvant setting.The panel focussed on

• the use of trastuzumab and other her2-targeted agents as neoadjuvant therapy in primary operable, locally advanced, and inflammatory breast cancer; and
• possible choices of chemotherapeutic regimens with trastuzumab.

The suggestions described here will continue to evolve as data from current and future trials with trastuzumab and other her2-targeted agents emerge.     

Consensus recommendations for the diagnosis and management of well-differentiated gastroenterohepatic neuroendocrine tumours: a revised statement from a Canadian National Expert Group

Well-differentiated neuroendocrine tumours (nets—previously called “carcinoid tumours”) are relatively rare tumours originating from the diffuse neuroendocrine system; they are found most often in the bronchial or gastrointestinal systems. In Canada, gastroenterohepatic nets represent less than 0.25% of oncology cases. Because of the relative rarity of these tumours, diagnostic and therapeutic approaches vary and are often based on individual physician experience. A number of European and North American groups have developed consensus guidelines for the diagnosis and management of well-differentiated gastroenterohepatic nets, and in 2006, Canadian consensus guidelines were published by a Canadian expert group. The updated and expanded current Canadian guidelines are based on a consensus meeting held in Paris, France, in 2008 and are based on the most current literature.     

Cost–utility of adjuvant zoledronic acid in patients with breast cancer and low estrogen levels

Background

Adjuvant zoledronic acid (za) appears to improve disease-free survival (dfs) in women with early-stage breast cancer and low levels of estrogen (lle) because of induced or natural menopause. Characterizing the cost–utility (cu) of this therapy could help to determine its role in clinical practice.

Methods

Using the perspective of the Canadian health care system, we examined the cu of adjuvant endocrine therapy with or without za in women with early-stage endocrine-sensitive breast cancer and lle. A Markov model was used to compute the cumulative costs in Canadian dollars and the quality-adjusted life-years (qalys) gained from each adjuvant strategy, discounted at a rate of 5% annually. The model incorporated the dfs and fracture benefits of adjuvant za. Probabilistic and one-way sensitivity analyses were conducted to examine key model parameters.

Results

Compared with a no-za strategy, adjuvant za in the induced and natural menopause groups was associated with, respectively, $7,825 and $7,789 in incremental costs and 0.46 and 0.34 in qaly gains for cu ratios of $17,007 and $23,093 per qaly gained. In one-way sensitivity analyses, the results were most sensitive to changes in the za dfs benefit. Probabilistic sensitivity analysis suggested a 100% probability of adjuvant za being a cost-effective strategy at a threshold of $100,000 per qaly gained.

Conclusions

Based on available data, adjuvant za appears to be a cost-effective strategy in women with endocrine-sensitive breast cancer and lle, having cu ratios well below accepted thresholds.     

Demographic profile and utilization statistics of a Canadian inpatient palliative care unit within a tertiary care setting

Background

Canadian data describing inpatient palliative care unit (pcu) utilization are scarce. In the present study, we performed a quality assessment of a 24-bed short-term pcu with a 3-months-or-less life expectancy policy in a tertiary care setting.

Methods

Using a retrospective chart review, we explored wait time (wt) for admission (May 2005 to April 2006), length of stay [los (February 2005 to January 2006)], and patient demographics.

Results

The wt data showed 508 referrals, with 242 resulting in admissions (92% malignant diagnoses) and 266 not (82% malignant). The most common malignancies in both groups were gastrointestinal, lung, and genitourinary. Median wt for admitted patients was 6 days, varying with referral source, such as the same hospital, home, or another hospital (6, 4, and 8.5 days respectively). Most admissions (93%) occurred in 21 or fewer days. Patient death (52%), admission to another pcu (25%), and declined offer (10%) were common reasons for no admission. Median los for 219 admitted patients was 19 days (range: 0–249 days). Most patients (94%) died in the pcu; a minority were discharged.

Conclusions

Many patients requiring pcu services are admitted within a few days of referral, especially patients with the least available support: those at home. However, half of the non-admitted patients die while waiting—a potential area for improvement. The los for admitted patients complied with the 3-month “expected lifespan” pcu policy. Results are significant, because ensuring quality of life for palliative care patients includes timely pcu access and sufficient los to address end-of-life needs.     

The use and effectiveness of temozolomide in children with central nervous system tumours: a survey from the Canadian Paediatric Brain Tumour Consortium

Objective

To describe the use of temozolomide (tmz) in Canadian children treated for brain tumours and to evaluate survival and predictors of survival for children treated with this agent.

Methods

A survey was conducted within the Canadian Paediatric Brain Tumour Consortium (cpbtc), a group of tertiary care centres in pediatric neuro-oncology (n = 16) in Canada that are involved in the treatment of children with central nervous system tumours.

Results

In 10 of the 16 participating pediatric oncology centres of the cpbtc, 137 children with brain tumours were treated with tmz between January 2000 and March 2006. Although 33% of the children were enrolled into a clinical trial, 67% were treated outside open studies. Most patients (72%) received tmz treatment on recurrence of their brain tumour (first or subsequent). The most commonly administered regimen was single-agent tmz 150–200 mg/m² administered on 5 consecutive days every 28 days. The median duration of tmz treatment was 141 days (range: 4–1102 days). Response data were provided for 127 of the 137 patients, of whom 6 showed a complete response. Sixteen patients experienced a minor or partial response, 53 had stable disease, and 52 had progressive disease. Of 32 patients alive at last follow-up, 19 had a diagnosis of low-grade glioma.

Conclusions

Temozolomide is used in a variety of pediatric brain tumours, often at the time of recurrence. The lack of insight into clear indications for this agent in pediatric brain tumours—used either alone or in combination therapy—may be a result of suboptimal design of phase i and ii studies and a lack of phase iii trials in the pediatric brain tumour population.     

High-grade glioma management and response assessment—recent advances and current challenges

The management of high-grade gliomas (hggs) is complex and ever-evolving. The standard of care for the treatment of hggs consists of surgery, chemotherapy, and radiotherapy. However, treatment options are influenced by multiple factors such as patient age and performance status, extent of tumour resection, biomarker profile, and tumour histology and grade. Follow-up cranial magnetic resonance imaging (mri) to differentiate treatment response from treatment effect can be challenging and affects clinical decision-making. An assortment of advanced radiologic techniques—including perfusion imaging with dynamic susceptibility contrast mri, dynamic contrast-enhanced mri, diffusion-weighted imaging, proton spectroscopy, mri subtraction imaging, and amino acid radiotracer imaging—can now incorporate novel physiologic data, providing new methods to help characterize tumour progression, pseudoprogression, and pseudoresponse. In the present review, we provide an overview of current treatment options for hgg and summarize recent advances and challenges in imaging technology.     

Cost-effectiveness of pazopanib compared with sunitinib in metastatic renal cell carcinoma in Canada

BackgroundIn Canada and elsewhere, pazopanib and sunitinib—tyrosine kinase inhibitors targeting the vascular endothelial growth factor receptors—are recommended as first-line treatment for patients with metastatic renal cell carcinoma (mrcc). A large randomized noninferiority trial of pazopanib versus sunitinib (comparz) demonstrated that the two drugs have similar efficacy; however, patients randomized to pazopanib experienced better health-related quality of life (hrqol) and nominally lower rates of non-study medical resource utilization.MethodsThe cost-effectiveness of pazopanib compared with sunitinib for first-line treatment of mrcc from a Canadian health care system perspective was evaluated using a partitioned-survival model that incorporated data from comparz and other secondary sources. The time horizon of 5 years was based on the maximum duration of follow-up in the final analysis of overall survival from the comparz trial. Analyses were conducted first using list prices for pazopanib and sunitinib and then by assuming that the prices of sunitinib and pazopanib would be equivalent.ResultsBased on list prices, expected costs were CA$10,293 less with pazopanib than with sunitinib. Pazopanib was estimated to yield 0.059 more quality-adjusted life-years (qalys). Pazopanib was therefore dominant (more qalys and lower costs) compared with sunitinib in the base case. In probabilistic sensitivity analyses, pazopanib was dominant in 79% of simulations and was cost-effective in 90%–100% of simulations at a threshold cost-effectiveness ratio of CA$100,000. Assuming equivalent pricing, pazopanib yielded CA$917 in savings in the base case, was dominant in 36% of probabilistic sensitivity analysis simulations, and was cost-effective in 89% of simulations at a threshold cost-effectiveness ratio of CA$100,000.ConclusionsCompared with sunitinib, pazopanib is likely to be a cost-effective option for first-line treatment of mrcc from a Canadian health care perspective.     

Improving access to cancer guidelines: feedback from health care professionals

PurposeWe examined access to locally developed and other available clinical practice guidelines (cpgs) for the management of cancer and evaluated how to improve uptake.MethodsA 12-question online survey was administered to 772 members of 12 multidisciplinary tumour teams in a Canadian provincial oncology program. The teams are composed of physicians, surgeons, nurses, allied health professionals, and researchers involved in the provision of cancer care across the province. Many of these individuals construct or provide input into the provincial cpgs. The questionnaires were administered online and were completed voluntarily.ResultsResponses were received from 232 individuals, a response rate of 30.1%. Most respondents (75.1%) indicated they actively referenced cpgs for cancer treatment. Of the 177 respondents who identified barriers to cpg access, 24.9% said that the cause was being too busy; 24.3% and 22.6% cited the user-unfriendliness of the Web site and a lack of awareness about the cpgs. When asked about innovative changes that could be made to improve access, the creation of cpg summary documents was identified as the most effective change (46.3%). The creation of summary documents was ranked highest by physicians, surgeons, and nurses.ConclusionsClinical practice guidelines are important tools for standardizing treatment protocols and improving outcomes in health care systems, but support for their use is variable among health care professionals. We have identified barriers to—and potential mitigating strategies for—more widespread access to cpgs by the various health professions involved in cancer care. Local creation of succinct and easily accessible cpgs was identified as the single most effective way to enhance access by health care professionals.     

Optimizing the management of her2-positive early breast cancer: the clinical reality

Breast cancer positive for her2 (human epidermal growth factor receptor 2) is associated with a poor prognosis for patients with both early-stage and metastatic breast cancer. Trastuzumab has been shown to be effective and is now considered the standard of care for early-stage patients with her2-positive breast cancer. In that population, trastuzumab has been studied in six randomized clinical trials. Overall, use of this agent leads to a significant reduction in risk of disease recurrence and improvement in overall survival. Despite the strong evidence for the use of trastuzumab in managing her2-positive early breast cancer (ebc), a number of clinical controversies remain. The authors of this paper undertook a review of the available scientific literature on adjuvant trastuzumab to produce practical considerations from Canadian oncologists. The panel focused their discussion on five key areas:

• Management of node-negative disease with tumours 1 cm or smaller in size
• Management of her2-positive ebc across the spectrum of the disease (that is, nodal and steroid hormone receptor status, tumour size)
• Timing of trastuzumab therapy with chemotherapy for early-stage disease: concurrent or sequential
• Treatment duration of trastuzumab for ebc
• The role of non-anthracycline trastuzumab-based regimens

     

Is clinical breast examination important for breast cancer detection?

BackgroundScreening clinical breast examination (cbe) is controversial; the use of cbe is declining not only as a screening tool, but also as a diagnostic tool. In the present study, we aimed to assess the value of cbe in breast cancer detection in a tertiary care centre for breast diseases.MethodsThis retrospective study of all breast cancers diagnosed between July 1999 and December 2010 at our centre categorized cases according to the mean of detection (cbe, mammography, or both). A cbe was considered “abnormal” in the presence of a mass, nipple discharge, skin or nipple retraction, edema, erythema, peau d’orange, or ulcers.ResultsDuring the study period, a complete dataset was available for 6333 treated primary breast cancers. Cancer types were ductal carcinoma in situ (15.3%), invasive ductal carcinoma (75.7%), invasive lobular carcinoma (9.0%), or others (2.2%). Of the 6333 cancers, 36.5% (n = 2312) were detected by mammography alone, 54.8% (n = 3470) by mammography and cbe, and 8.7% (n = 551) by physician-performed cbe alone (or 5.3% if considering ultrasonography). Invasive tumours diagnosed by cbe alone were more often triple-negative, her2-positive, node-positive, and larger than those diagnosed by mammography alone (p < 0.05).ConclusionsA significant number of cancers would have been missed if cbe had not been performed. Compared with cancers detected by mammography alone, those detected by cbe had more aggressive features. Clinical breast examination is a very low-cost test that could improve the detection of breast cancer and could prompt breast ultrasonography in the case of a negative mammogram.     

A Canadian consensus on the management of newly diagnosed and relapsed acute promyelocytic leukemia in adults

The use of all-trans-retinoic acid (atra) and anthracyclines (with or without cytarabine) in the treatment of acute promyelocytic leukemia (apl) has dramatically changed the management and outcome of the disease over the past few decades. The addition of arsenic trioxide (ato) in the relapsed setting—and, more recently, in reduced-chemotherapy or chemotherapy-free approaches in the first-line setting—continues to improve treatment outcomes by reducing some of the toxicities associated with anthracycline-based approaches. Despite those successes, a high rate of early death from complications of coagulopathy remains the primary cause of treatment failure before treatment begins. In addition to that pressing issue, clarity is needed about the use of ato in the first-line setting and the role of hematopoietic stem-cell transplantation (hsct) in the relapsed setting. The aim for the present consensus was to provide guidance to health care professionals about strategies to reduce the early death rate, information on the indications for hsct and on the use of ato in induction and consolidation in low-to-intermediate–risk and high-risk apl patients.     

Radiation costing methods: a systematic review

ObjectiveCosts for radiation therapy (rt) and the methods used to cost rt are highly diverse across the literature. To date, no study has compared various costing methods in detail. Our objective was to perform a thorough review of the radiation costing literature to identify sources of costs and methods used.MethodsA systematic review of Ovid medline, Ovid oldmedline, embase, Ovid HealthStar, and EconLit from 2005 to 23 March 2015 used search terms such as “radiation,” “radiotherapy,” “neoplasm,” “cost,” “ cost analysis,” and “cost benefit analysis” to locate relevant articles. Original papers were reviewed for detailed costing methods. Cost sources and methods were extracted for papers investigating rt modalities, including three-dimensional conformal rt (3D-crt), intensity-modulated rt (imrt), stereotactic body rt (sbrt), and brachytherapy (bt). All costs were translated into 2014 U.S. dollars.ResultsMost of the studies (91%) reported in the 33 articles retrieved provided rt costs from the health system perspective. The cost of rt ranged from US$2,687.87 to US$111,900.60 per treatment for imrt, followed by US$5,583.28 to US$90,055 for 3D-crt, US$10,544.22 to US$78,667.40 for bt, and US$6,520.58 to US$19,602.68 for sbrt. Cost drivers were professional or personnel costs and the cost of rt treatment. Most studies did not address the cost of rt equipment (85%) and institutional or facility costs (66%).ConclusionsCosting methods and sources were widely variable across studies, highlighting the need for consistency in the reporting of rt costs. More work to promote comparability and consistency across studies is needed.     

Novel agents and associated toxicities of inhibitors of the pi3k/Akt/mtor pathway for the treatment of breast cancer

The pi3k/Akt/mtor (phosphatidylinositol 3 kinase/ Akt/mammalian target of rapamycin) signalling pathway is an established driver of oncogenic activity in human malignancies. Therapeutic targeting of this pathway holds significant promise as a treatment strategy. Everolimus, an mtor inhibitor, is the first of this class of agents approved for the treatment of hormone receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer. Everolimus has been associated with significant improvements in progression-free survival; however, it is also associated with increased toxicity related to its specific mechanism of action.

Methods

A comprehensive review of the literature conducted using a focused medline search was combined with a search of current trials at http://ClinicalTrials.gov/. Summary tables of the toxicities of the various classes of pi3k/Akt/mtor inhibitors were created. A broad group of Canadian health care professionals was assembled to review the data and to produce expert opinion and summary recommendations for possible best practices in managing the adverse events associated with these pathway inhibitors.

Results

Differing toxicities are associated with the various classes of pi3k/Akt/mtor pathway inhibitors. The most common unique adverse events observed in everolimus clinical trials in breast cancer include stomatitis (all grades: approximately 60%), noninfectious pneumonitis (15%), rash (40%), hyperglycemia (15%), and immunosuppression (40%). To minimize grades 3 and 4 toxicities and to attempt to attain optimal outcomes, effective management of those adverse events is critical. Management should be interdisciplinary and should use approaches that include education, early recognition, active intervention, and potentially prophylactic strategies.

Discussion

Everolimus likely represents the first of many complex oral targeted therapies for the treatment of breast cancer. Using this agent as a template, it is essential to establish best practices involving and integrating multiple disciplines for the management of future pi3k/Akt/mtor signalling pathway inhibitors.