Therapy For Early-stage Breast Cancer Research Articles

The Pattern of Use of Hypofractionated Radiation Therapy for Early-Stage Breast Cancer in New South Wales, Australia, 2008 to 2012

Increasing phase 3 evidence has been published about the safety and efficacy of hypofractionated radiation therapy, in comparison with standard fractionation, in early-stage, node-negative breast cancer. However, uptake of hypofractionation has not been universal. The aim of this study was to investigate the hypofractionation regimen variations in practice across public radiation oncology facilities in New South Wales (NSW). Patients with early breast cancer registered in the NSW Clinical Cancer Registry who received radiation therapy for early-stage breast cancer in a publicly funded radiation therapy department between 2008 and 2012 were identified. Data extracted and analyzed included dose and fractionation type, patient age at first fraction, address (for geocoding), year of diagnosis, year of treatment, laterality, and department of treatment. A logistic regression model was used to identify factors associated with fractionation type. Of the 5880 patients fulfilling the study criteria, 3209 patients (55%) received standard fractionation and 2671 patients (45%) received hypofractionation. Overall, the use of hypofractionation increased from 37% in 2008 to 48% in 2012 (range, 7%-94% across departments). Treatment facility and the radiation oncologist prescribing the treatment were the strongest independent predictors of hypofractionation. Weaker associations were also found for age, tumor site laterality, year of treatment, and distance to facility. Hypofractionated regimens of whole breast radiation therapy have been variably administered in the adjuvant setting in NSW despite the publication of long-term trial results and consensus guidelines. Some factors that predict the use of hypofractionation are not based on guideline recommendations, including lower rates of left-sided treatment and increasing distance from a treatment facility.

An observational study to examine changes in metabolic syndrome components in patients with breast cancer receiving neoadjuvant or adjuvant chemotherapy.

BACKGROUNDThe authors sought to determine the effect of chemotherapy on the development of metabolic syndrome (MetS) in premenopausal and postmenopausal women undergoing (neo)adjuvant therapy for early‐stage breast cancer.METHODSA total of 86 women with early‐stage (AJCC stage I‐III) breast cancer who were free from clinically diagnosed MetS (defined as 3 of 5 components of MetS) were prospectively tested for the presence of the 5 components of MetS within 1 week before initiating and after completing (neo)adjuvant chemotherapy. The 5 components of MetS measured were waist circumference; blood pressure; and fasting levels of blood glucose, triglycerides, and high‐density lipoprotein cholesterol. Anthropometrics (body weight, percentage body fat, fat mass), lipid profile (total cholesterol, low‐density lipoprotein cholesterol), glucose metabolism (insulin, homeostatic model assessment of insulin resistance, glycated hemoglobin), and inflammation (C‐reactive protein) also were examined before initiating and after completing treatment.RESULTSThe current study included 46 premenopausal and 40 postmenopausal women. All individual MetS components and the overall MetS score were found to be statistically significantly increased (P<.01) after chemotherapy. Body weight, percentage body fat, fat mass, lipids, glucose metabolism, and inflammation also were found to be statistically significantly increased (P<.01).CONCLUSIONSA 12‐week to 18‐week course of chemotherapy appears to statistically significantly increase MetS and related anthropometrics, biomarkers of glucose metabolism, and inflammation in patients with early‐stage breast cancer with no preexisting MetS. Lifestyle interventions such as diet and exercise may be preventive approaches for use during chemotherapy to reduce the onset of MetS in patients with breast cancer. Cancer 2016. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. Cancer 2016;122:2646–2653. © 2016 American Cancer Society.

Association of Locoregional Control With High Body Mass Index in Women Undergoing Breast Conservation Therapy for Early-Stage Breast Cancer

Obesity, as measured by the body mass index (BMI), is a risk factor for distant recurrence and decreased survival in breast cancer. We sought to determine whether the BMI correlated with local recurrence and reduced survival in a cohort of predominantly obese women treated with breast conservation therapy. From 1998 to 2010, 154 women with early-stage invasive breast cancer and 39 patients with ductal carcinoma in situ underwent prone whole breast irradiation. Cox proportional hazards regression, Kaplan-Meier methods with the log-rank test, and multivariate analysis were used to explore the association of the outcomes with the BMI. The median patient age was 60years, and the median follow-up duration was 73months. The median BMI was 33.2kg/m(2); 91% of the patients were overweight (BMI ≥25kg/m(2)) and 69% of the patients were clinically obese (BMI ≥30kg/m(2)). The BMI was significantly associated with the locoregional recurrence-free interval for patients with invasive cancer and ductal carcinoma in situ (hazard ratio [HR], 1.09; P=.047). Also, a trend was seen for increased locoregional recurrence with a higher BMI (P=.09) for patients with invasive disease, which was significant when examining the outcomes with a BMI stratified by the median value of 33.2kg/m(2) (P=.008). A greater BMI was also significantly associated with decreased distant recurrence-free interval (HR, 1.09; P=.011) and overall survival (HR, 1.09; P=.004); this association remained on multivariate analysis (distant recurrence-free interval, P=.034; overall survival, P=.0007). These data suggest that the BMI might affect the rate of locoregional recurrence in breast cancer patients. A higher BMI predicted a worse distant recurrence-free interval and overall survival. The present investigation adds to the increasing evidence that BMI is an important prognostic factor in early-stage breast cancer treated with breast conservation therapy.

Disparities in Use of Human Epidermal Growth Hormone Receptor 2-Targeted Therapy for Early-Stage Breast Cancer.

Trastuzumab is a key component of adjuvant therapy for stage I to III human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The rates and patterns of trastuzumab use have never been described in a population-based sample. The recent addition of HER2 information to the SEER-Medicare database offers an opportunity to examine patterns of trastuzumab use and to evaluate possible disparities in receipt of trastuzumab. We examined a national cohort of Medicare beneficiaries with incident stage I to III HER2-positive breast cancer diagnosed in 2010 and 2011 (n = 1,362). We used insurance claims data to track any use of trastuzumab in the 12 months after diagnosis as well as to identify chemotherapy drugs used in partnership with trastuzumab. We used modified Poisson regression analysis to evaluate the independent effect of race on likelihood of receiving trastuzumab by controlling for clinical need, comorbidity, and community-level socioeconomic status. Overall, 50% of white women and 40% of black women received some trastuzumab therapy. Among women with stage III disease, 74% of whites and 56% of blacks received trastuzumab. After adjustment for tumor characteristics, poverty, and comorbidity, black women were 25% less likely to receive trastuzumab within 1 year of diagnosis than white women (risk ratio, 0.745; 95% CI, 0.60 to 0.93). Approxemately one half of patients 65 years of age and older with stage I to III breast cancer do not receive trastuzumab-based therapy, which includes many with locally advanced disease. Significant racial disparities exist in the receipt of this highly effective therapy. Further research that identifies barriers to use and increases uptake of trastuzumab could potentially improve recurrence and survival outcomes in this population, particularly among minority women.

The association between pre-treatment occupational skill level and mood and symptom burden in early-stage, postmenopausal breast cancer survivors during the first year of anastrozole therapy.

Previous research has explored occupational activity of breast cancer survivors but has not examined the influence of occupational level on symptoms prospectively. The purpose of this study was to examine the relationship between occupational classification and changes in mood and symptom burden for postmenopausal breast cancer survivors during the first year of anastrozole therapy. This was an exploratory secondary analysis in 49 postmenopausal women receiving anastrozole therapy for early-stage breast cancer. Participants reported their occupation at baseline and completed self-report questionnaires measuring mood and symptom burden at baseline, 6months, and 12months. Occupation was classified according to four major skill levels delineated by the International Standard Classification of Occupations (ISCO). Breast cancer survivors employed at occupational skill levels 1 through 3 reported significantly higher depressive symptoms, fatigue, and total symptoms on average than those employed at ISCO skill level 4. After adjusting for multiple comparisons, this pattern remained for the musculoskeletal, vasomotor, and gastrointestinal symptom subscales. Breast cancer survivors employed at lower skill levels (i.e., ISCO 1-3) reported poorer mood and greater symptom burden than breast cancer survivors employed at a higher skill level (i.e., ISCO 4). Assessing baseline occupation of occupationally active breast cancer survivors may improve understanding of the association between types of occupations and mood and symptom trajectories and may inform development of interventions to mitigate symptom severity in order to help breast cancer survivors maintain optimal occupational function and adherence to therapy.

Establishing achievable benchmarks for quality improvement in systemic therapy for early-stage breast cancer.

263 Background: Setting realistic targets for performance on quality indicators (QI) is a consistent challenge in quality improvement. The purpose of this study was to utilize administrative data to define achievable targets for QI in the early stage breast cancer (EBC) population in relation to systemic therapy (ST) delivery based on best performers. Methods: Deterministically linked administrative healthcare databases were used to identify EBC cases diagnosed 2006 – 2010 in Ontario, Canada. Panel of previously established QIs for systemic therapy was applied to patients who met eligibility criteria for the individual indicators. Institutions with less than 10 eligible patients for a specific indicator were excluded. An empiric benchmark was defined as the proportion of patients meeting the indicator from institutions accounting for the top decile of eligible patients. Results: We identified 28,303 EBC patients who received surgery of which 12,252 received adjuvant chemotherapy. Benchmark results are summarized in Table. Conclusions: Many institutions fell considerably below the benchmark. Further analysis of institution-level drivers of high quality care is required to help characterize high performing institutions. [Table: see text]

Neoadjuvant therapy for early-stage breast cancer: the clinical utility of pertuzumab.

Approximately 20% of breast cancer patients harbor tumors that overexpress human epidermal growth factor receptor 2 (HER2; also known as ErbB2), a receptor tyrosine kinase that belongs to the epidermal growth factor receptor family of receptor tyrosine kinases. HER2 amplification and hyperactivation drive the growth and survival of breast cancers through the aberrant activation of proto-oncogenic signaling systems, particularly the Ras/MAP kinase and PI3K/AKT pathways. Although HER2-positive (HER2+) breast cancer was originally considered to be a highly aggressive form of the disease, the clinical landscape of HER2+ breast cancers has literally been transformed by the approval of anti-HER2 agents for adjuvant and neoadjuvant settings. Indeed, pertuzumab is a novel monoclonal antibody that functions as an anti-HER2 agent by targeting the extracellular dimerization domain of the HER2 receptor; it is also the first drug to receive an accelerated approval by the US Food and Drug Administration for use in neoadjuvant settings in early-stage HER2+ breast cancer. Here, we review the molecular and cellular factors that contribute to the pathophysiology of HER2 in breast cancer, as well as summarize the landmark preclinical and clinical findings underlying the approval and use of pertuzumab in the neoadjuvant setting. Finally, the molecular mechanisms operant in mediating resistance to anti-HER2 agents, and perhaps to pertuzumab as well, will be discussed, as will the anticipated clinical impact and future directions of pertuzumab in breast cancer patients.

Cardiac Surveillance Guidelines for Trastuzumab-Containing Therapy in Early-Stage Breast Cancer: Getting to the Heart of the Matter.

Trastuzumab-containing regimens for breast cancer have significantly improved survival both in the early-stage and metastatic settings.1-8 Nevertheless, given the early signals of cardiotoxicity, a prevailing concern exists regarding the risk of cardiotoxicity, defined as a decline in left ventricular ejection fraction (LVEF) both asymptomatic and symptomatic. This concern that LVEF decline would be an early and actionable surrogate for subsequent development of congestive heart failure (CHF) led to the design and implementation of specific eligibility criteria and LVEF surveillance guidelines for the pivotal randomized adjuvant trials. These guidelines were subsequently adopted as the standard of care. However, it is increasingly unclear whether these specific recommendations are justified for all patients. Resolution of this matter is critical for our community because adherence to these guidelines was recently proposed as a quality metric.9 This issue raises the general question of the level of evidence needed to accept a toxicity screening schedule as a quality indicator. If following these guidelines is not associated with improved outcomes, then adherence to them as a quality metric should be challenged. Cardiotoxicity screening can serve to illuminate this issue. Here, we review the historical events that led to the development of the current guidelines and highlight critical knowledge gaps with regard to the benefits of screening and intervention.

Disparities in Use of Human Epidermal Growth Hormone Receptor 2–Targeted Therapy for Early-Stage Breast Cancer

Disparities in Use of Human Epidermal Growth Hormone Receptor 2–Targeted Therapy for Early-Stage Breast Cancer

External beam boost versus interstitial high-dose-rate brachytherapy boost in the adjuvant radiotherapy following breast-conserving therapy in early-stage breast cancer: a dosimetric comparison.

PurposeThis study aims to compare the dosimetric data of local tumor's bed dose escalation (boost) with photon beams (external beam radiation therapy – EBRT) versus high-dose-rate interstitial brachytherapy (HDR-BT) after breast-conserving treatment in women with early-stage breast cancer.Material and methodsWe analyzed the treatment planning data of 136 irradiated patients, treated between 2006 and 2013, who underwent breast-conserving surgery and adjuvant whole breast irradiation (WBI; 50.4 Gy) and boost (HDR-BT: 10 Gy in one fraction [n = 36]; EBRT: 10 Gy in five fractions [n = 100]). Organs at risk (OAR; heart, ipsilateral lung, skin, most exposed rib segment) were delineated. Dosimetric parameters were calculated with the aid of dose-volume histograms (DVH). A non-parametric test was performed to compare the two different boost forms.ResultsThere was no difference for left-sided cancers regarding the maximum dose to the heart (HDR-BT 29.8% vs. EBRT 29.95%, p = 0.34). The maximum doses to the other OAR were significantly lower for HDR-BT (Dmax lung 47.12% vs. 87.7%, p < 0.01; rib 61.17% vs. 98.5%, p < 0.01; skin 57.1% vs. 94.75%, p < 0.01; in the case of right-sided breast irradiation, dose of the heart 6.00% vs. 16.75%, p < 0.01).ConclusionsCompared to EBRT, local dose escalation with HDR-BT presented a significant dose reduction to the investigated OAR. Only left-sided irradiation showed no difference regarding the maximum dose to the heart. Reducing irradiation exposure to OAR could result in a reduction of long-term side effects. Therefore, from a dosimetric point of view, an interstitial boost complementary to WBI via EBRT seems to be more advantageous in the adjuvant radiotherapy of breast cancer.

The Use of 3-D Ultrasound Imaging System in Hypofractionated Radiation Therapy for Early-Stage Breast Cancer After Breast Conservation Therapy

Purpose/Objective(s): Our institute initiated a clinical study of radical accelerated partial breast irradiation (APBI) for stage I breast cancer using carbon-ion radiation therapy (C-ion RT). The purpose of this report is to evaluate preliminary treatment results. Materials/Methods: Candidates for clinical trial are patients with low-risk stage I breast cancer who are suitable for APBI in ASTRO consensus statement (2009). Tumors located more than 5 mm from the skin and no prior treatment are also eligibility criteria. A dose escalation study was designed as a phase I clinical trial with the dose level based on our experience. Total dose is 48.0 GyE, 52.8 GyE, and 60.0 GyE in 4 fractions within one week, at fraction sizes of 12 GyE, 13.2 GyE, and 15 GyE, respectively. In phase I, patients plan to undergo surgery for pathological evaluation 90 days after C-ion RT and then receive endocrine therapy. In phase II, patients have C-ion RT at recommended dose and then receive endocrine therapy. Treatment posture is supine, with an immobilization cast, fixation body and breast shells. Three-field C-ion beams with 290 MeV/n energy is used by means of passive broad beam methods using individual collimators and a compensation bolus absorber. Irradiation is performed using respiratory gating. Primary end points are early normal tissue reaction and tumor control at recommended dose. Secondary end points are CR rate, late normal tissue reaction, cosmetic outcome, diseasefree survival, and overall survival. Patients with stage I breast cancer desiring to receive C-ion RT but ineligible to enroll in the clinical trial due to variance or refusal to enroll in the clinical trial, although certain reasons make them unsuitable for standard treatment, were treated by “C-ion RT general treatment protocol for localized solid tumors” with the patient’s and institute’s agreement. The first 2 patients of this “general protocol” were treated by 52.8 GyE and the others by 60 GyE. The patients were suitable for endocrine therapy after RT. Results: From April 2013 to February 2015, 3 cases of 48 GyE, 3 cases of 52.8 GyE and 1 case of 60 GyE of phase I were treated, and 2 cases of 52.8 GyE and 5 cases of 60 GyE of “general protocol” were treated. Patients’ age ranged from 44 to 81 years, median 66 years. Tumor size was 4 to 20 mm, median 12 mm. The follow-up period ranged from 1 to 22 months, median 9 months. No adverse reactions in normal tissue were observed except for grade 1 skin reaction of CTC-AE v4 in 5 cases. At the time of analysis, 6 patients underwent surgery and 2 of them reached pathological CR. Of the “general protocol” patients, 4 reached CR, 2 reached PR, and 1 developed PD on MRI. The PD patient with triple negative subtype tumor was successfully salvaged by surgery. Conclusion: C-ion RT for patients with stage I breast cancer seems useful, and the significance of continuing the study is recognized. Author Disclosure: K. Karasawa: None. T. Omatsu: None. S. Fukuda: None. T. Kamada: None. N. Yamamoto: None. T. Ishikawa: None. A. Arakawa: None. M. Saito: None.

Stereotactic Body Radiation Therapy for Early-Stage Breast Cancer Using a Robotic Linear Accelerator

Stereotactic Body Radiation Therapy for Early-Stage Breast Cancer Using a Robotic Linear Accelerator

Intraoperative Radiation Therapy Versus Whole-Breast External Beam Radiation Therapy in Early-Stage Breast Cancer: A Systematic Review and Meta-Analysis

Intraoperative Radiation Therapy Versus Whole-Breast External Beam Radiation Therapy in Early-Stage Breast Cancer: A Systematic Review and Meta-Analysis

Meta-Analysis of Standard Versus Hypofractionated Whole-Breast Radiation Therapy as Part of Breast Conserving Therapy for Early-Stage Breast Cancer

Meta-Analysis of Standard Versus Hypofractionated Whole-Breast Radiation Therapy as Part of Breast Conserving Therapy for Early-Stage Breast Cancer

Socioeconomic Factors Impact Probability of Receiving Radiation As Part of Breast Conserving Therapy for Early-Stage Breast Cancer

Socioeconomic Factors Impact Probability of Receiving Radiation As Part of Breast Conserving Therapy for Early-Stage Breast Cancer

Favorable Proliferative Response Using Ki-67 in Patients Prospectively Treated With Preoperative Accelerated Partial-Breast Radiation Therapy for Early-Stage Breast Cancer

Forest School of Medicine. J. Strasser: None. G. Enevold: None. M. Naughton: Committee leadership; Alliance for Clinical Trials in Oncology. K.E. Weaver: None. K. Baglan: None. D. Bryant: None. C. Langefeld: None. T. Lad: None. L. Lee: None. G.P. Rine: None. A.E. Curtis: None. C.D. Koprowski: None. W.V. Tomlinson: None. G.J. Lesser: Employee; Wake Forest School of Medicine. Leader of research program; Wake Forest NCORP. E.G. Shaw: None. J. Hu: None.

Definitive Radiation Therapy for Early-Stage Breast Cancer: Dosimetric Feasibility of Stereotactic Ablative Radiosurgery (SABR) for Intact Breast Tumors

Definitive Radiation Therapy for Early-Stage Breast Cancer: Dosimetric Feasibility of Stereotactic Ablative Radiosurgery (SABR) for Intact Breast Tumors

Zoledronic acid prevents the tumor-promoting effects of mesenchymal stem cells via MCP-1 dependent recruitment of macrophages.

Zoledronic acid (ZA) has been tested in clinical trials as an additive therapy for early-stage breast cancer. However, the mechanism by which ZA exerts its antitumor activity is still unclear. The aim of this study is to investigate whether the prevention of tumor growth by ZA is through regulating the mesenchymal stem cells (MSC)-monocyte chemotactic protein 1 (MCP-1)-macrophages axis in the tumor microenvironment. To address this issue, MDA-MB-231-FLUC human breast cancer cells were cultured and injected either alone, or coupled with MSC into the mammary fat pads of nude mice. MSC were treated with either ZA or untreated. Tumor growth was determined by using an in vivo bioluminescence imaging (BLI) and the tumor-associated macrophages (TAMs) in tumor tissues were immunohistochemically analyzed by using CD206 antibody. The effects of ZA on the cytokine related gene expression of MSC were assessed by using real-time PCR. In this study, we found that ZA-treated mice showed a significant delay in tumor growth. In addition, our data revealed that ZA weakened the ability of MSC to promote tumor growth by impairing TAMs recruitment and tumor vascularization. Furthermore, it was found that ZA decreased MCP-1 expression of MSC, and therefore reduced the recruitment of TAMs to the tumor sites and hence inhibited the tumor growth. Altogether, our study demonstrated ZA can prevent the tumor-promoting effects of MSC. The antitumor effects of ZA were caused by decreasing the MCP-1 expression of MSC, which further decreased the infiltration of TAMs into tumor sites, and therefore inhibited the tumor growth.

Abstract 3327: Metabolomics: Potential molecular mechanisms of radiotherapy (RT)-related normal tissue toxicities in breast cancer

Abstract Breast cancer is the most frequently diagnosed cancer in women and the second leading cause of cancer death in American women. Clinical guidelines recommend that when breast-conserving surgery is provided as a primary therapy for early-stage breast cancer, RT should follow to improve clinical outcome. Although well tolerated by most patients, even with improved RT technology, breast cancer patients experience moist desquamation as early adverse skin reactions. To elucidate the molecular mechanisms involved in RT-related normal tissure toxicity, global metabolomic profiles were determined in urine samples comparing across paired pre-RT and post-RT samples from 60 breast cancer patients exhibiting low (n = 30) or high (n = 30) skin toxicity in response to RT. The extracted samples were split into equal parts for analysis on the GC/MS and LC/MS platforms. The dataset comprises a total of 478 compounds of known identity. Preliminary data suggest that pre-RT glucose and a variety of derivatives linked to the pentose phosphate pathway, such as ribulose, or the consumption of pyruvate in the mitochondrial tricarboxylic acid cycle, including citrate and succinate, were significantly elevated in the high toxicity group. Multiple metabolites derived from the oxidation of aromatic compounds such as amino acids and dietary polyphenolics - vanillate, 3-hydromandelate, tyramine, 3-methoxy-4-hydroxyphenylglycol, and 2-hydroxyphenylacetate - were elevated in a trending or significant fashion at the pre-RT baseline in the high toxicity relative to the low toxicity group. Pre-RT ascorbate depletion and accumulation of tobacco metabolites were associated with radiation sensitivity. Ascorbate was significantly decreased at baseline in the high toxicity group and its pre-RT levels were negatively correlated with post-RT skin toxicity. Nicotine derivatives were only detected in 12% of the pre- and post-RT samples but their presence seemed to be a risk factor that could predispose smokers to unfavorable outcomes during radiation therapy. Histamine breakdown markers provided an indication of a heightened inflammatory activity in individuals who experienced toxicity as suggested that anti-histamines might be useful to prevent sensitivity. Our preliminary data suggest the potential application of metabolomics in predicting and monitoring RT-related normal tissue toxicities; future larger studies are warranted to confirm out promising findings and identify targeted metabolic pathways for effective intervention. Citation Format: Jennifer J. Hu, Eunkyung Lee, Cristiane Takita, Jean L. Wright, Omar L. Nelson. Metabolomics: Potential molecular mechanisms of radiotherapy (RT)-related normal tissue toxicities in breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3327. doi:10.1158/1538-7445.AM2015-3327

Optimal Systemic Therapy for Early Breast Cancer in Women: A Clinical Practice Guideline

The Breast Cancer Disease Site Group of Cancer Care Ontario identified the need for new guidelines for the adjuvant systemic therapy of early-stage breast cancer. The specific question to be addressed was "What is the optimal adjuvant systemic therapy for female patients with early-stage operable breast cancer, when patient and disease factors are considered?" A systematic review was prepared based on literature searches conducted using the medline and embase databases for the period January 2008 to March 5, 2012, and updated to May 12, 2014. Guidelines were located from that search, from the Standards and Guidelines Evidence directory of cancer guidelines, and from the Web sites of major guideline organizations. The literature located was subdivided into the broad categories of chemotherapy, hormonal therapy, and therapy targeted to her2 (human epidermal growth factor receptor 2). Although several of the systemic therapies discussed in this guideline can be considered in the neoadjuvant setting, the review focused on trials with rates of disease-free and overall survival as endpoints and thus excluded several trials that used pathologic complete response as a primary endpoint. Based on the systematic review, the working group drafted recommendations on the use of chemotherapy, hormonal therapy, and targeted therapy; based on their professional experience, they also drafted recommendations on patient and disease characteristics and recurrence risk. The literature review and draft recommendations were circulated to a consensus panel of medical oncologists who had expertise in breast cancer and who represented the regions of Ontario. Items without initial consensus were discussed at an in-person consensus meeting held in Toronto, November 23, 2012. The final recommendations are those for which consensus was reached before or at the meeting. Some of the key evidence was revised after the updated literature search. Evidence reviews for systemic chemotherapy, endocrine therapy, and targeted therapy for her2-positive disease are reported in separate articles in this supplement. The full three-part 1-21 evidence-based series, including complete details of the development and consensus processes, can be found on the Cancer Care Ontario Web site at https://www.cancercare.on.ca/toolbox/qualityguidelines/diseasesite/breast-ebs.