Mary Anne Fenton

Frequent Pathologic Complete Responses in Aggressive Stages II to III Breast Cancers With Every-4-Week Carboplatin and Weekly Paclitaxel With or Without Trastuzumab: A Brown University Oncology Group Study

PURPOSE To evaluate the efficacy and safety of neoadjuvant carboplatin and weekly paclitaxel +/- weekly trastuzumab in resectable and locally advanced breast cancer. PATIENTS AND METHODS Women with stages IIA to IIIB disease received carboplatin dosed by six times the area under the curve every 4 weeks and paclitaxel 80 mg/m(2) weekly for 16 weeks, and weekly trastuzumab was added for human epidermal growth factor receptor 2 (HER2) -positive status. The primary end point was the pathologic complete response (pCR) rate, defined as the absence of invasive disease in the breast and axillary nodes. Postoperative therapies were at the discretion of the treating physicians. RESULTS Fifty-five patients were enrolled, and of these 43 had resectable disease. The median age was 54 years (range, 31 to 74 years). Treatment was well tolerated; there were no episodes of febrile neutropenia or grade 4 thrombocytopenia, and there were only two instances of grade 3 peripheral neuropathy. Overall, the pCR rate was 45%. The pCR rate was 43% (95% CI, 28% to 58%) in patients with resectable disease. Higher pCR rates occurred in patients with HER2-positive tumors (76% v 31% for HER2-negative tumors; P = .003), with estrogen receptor (ER) -negative tumors (75% v 27% for ER-positive tumors; P = .001), or with triple-negative tumors (67% v 12% ER-positive and HER2-negative tumors; P = .002). At a median of 28 months postoperation, recurrence-free survival (RFS) was 88.7%. If patients with ER-positive and HER2-negative tumors are excluded from analysis, patients who achieved a pCR were less likely to experience disease recurrence (RFS, 86%) than those who did not achieve a pCR (RFS, 75%). CONCLUSION Neoadjuvant carboplatin and weekly paclitaxel +/- trastuzumab achieve high pCR rates in patients with HER2-positive and triple-negative disease without exposure to an anthracycline. Preliminary RFS results are encouraging but are likely influenced by adjuvant therapy received. Additional study of this regimen in high-risk patients is warranted.

Recruitment Strategies for a Home-Based Physical Activity Intervention for Breast Cancer Patients

Recruiting cancer patients for randomized trials investigating psychosocial interventions presents several unique challenges. This paper describes the challenges and yields for different recruitment methods used in Moving Forward, a randomized trial of a home-based moderate-intensity physical activity program for early-stage breast cancer survivors. Recruitment methods included letters sent to patients by their oncologists, direct referrals from oncologists, in-person recruitment in oncology clinics, referrals from nurses and medical assistants, passive recruitment, other mailings, and community outreach strategies. Of the 424 screenings completed, 86 (20.3%) participants were randomized. Physician letters yielded the greatest number of initial screenings (147; 34.7%) and participants randomized (28; 32.5%). In-person recruitment also proved to be a productive recruitment strategy; 14 (16.3%) of the participants were recruited via this strategy. Community outreach efforts did not provide as great a yield and were labor intensive. We discuss suggestions for recruitment of cancer patients in future trials.

Total Survivin and acetylated Survivin correlate with distinct molecular subtypes of breast cancer.

Global gene expression profiling studies led to the recent classification of breast cancer into 4 distinct molecular subtypes including luminal, human epidermal growth factor receptor 2 enriched, basal like, and unclassified. Here, we used immunohistochemistry to evaluate expression of the antiapoptotic protein Survivin and its recently described acetylated form, Survivin acetyl129, in normal breast tissue and in 226 primary breast tumors of different molecular subtypes. Correlation of Survivin expression with molecular markers and its impact on patient outcomes were analyzed. Eighty-four percent of basal-like tumors expressed high levels of total Survivin, whereas 52% of luminal tumors expressed high levels of acetylated Survivin (P < .001). Overall survival (91%) for tumors expressing low levels of total Survivin was better than that for tumors expressing high levels of total Survivin (72%, P = .02), whereas the reverse was true for tumors expressing acetylated Survivin. In hierarchical cluster analysis, total Survivin clustered with basal marker expression, whereas acetylated Survivin clustered with luminal marker expression. In multivariate analysis, high total Survivin expression was an independent predictor of worse overall survival in patients with breast cancer (relative risk, 11; P < .01). These data indicate that high levels of total Survivin predict poor outcome in patients with grade 3 invasive ductal carcinoma and correlate directly with a basal-like phenotype. In contrast, high expression of the acetylated form of the protein associates with a favorable outcome and preferentially correlates with luminal-type tumors. Survivin likely has different functions in distinct breast cancer subtypes, and diagnostic strategies that incorporate immunohistochemical markers that detect both Survivin forms may help better strategize patient risk and direct therapy.

Assessment of the effectiveness of a prechemotherapy teaching session: A Brown University Oncology Group study.

260 Background: Pre-chemotherapy teaching sessions, often coordinated by nursing personnel, are an opportunity to educate patients on treatment side effects, schedule, medications for toxicities such as nausea, and how to contact the oncology team if adverse events develop. Our institution provides a structured 60-minute nurse-coordinated pre-chemotherapy teaching session. The aims of this study were to evaluate whether pre-chemotherapy teaching sessions improve patient knowledge, preparedness, and anxiety in relation to chemotherapy. METHODS Patients were offered the opportunity to participate in the study after their medical oncologist had reviewed their treatment regimen. After informed consent was obtained, participants were administered a 10-question survey assessing knowledge of treatment adverse effects, treatment schedule, management of complications, accessing their medical team, and patient anxiety. Subjects then participated in a pre-chemotherapy teaching session with an oncology nurse. The survey was readministered when patients returned on day 1, cycle 1 of treatment and on day 1, cycle 2. The questionnaire used a 1 to 4 rating scale (1=no knowledge, 2= minimally informed, 3= reasonably informed, 4= well informed). A pre-defined mean change of 1 on the rating scale was considered to be clinically significant. Paired one-sided t-tests were performed to evaluate the mean change in groups between each of the three surveys. p values <0.05 were considered statistically significant. RESULTS At the time of analysis, 78 patients had completed a pre-chemotherapy teaching session and all three surveys. After participating in a teaching session, there was an increase in patients perceived knowledge of side effects (mean score 2.3 vs. 3.5, p<0.001), knowledge of the treatment schedule (mean score 2.4 vs. 3.5, p<0.001) and medications to prevent nausea (mean score of 1.4 vs. 3.1, p <0.001). There was also a statistically significant reduction in patient anxiety in relation to treatment, p< 0.001. CONCLUSIONS These results show that a nurse-coordinated, pre-chemotherapy teaching session increases patient knowledge and reduces anxiety regarding their upcoming treatment.

Breast cancer genetic risk evaluation and referral for assessment.

75 Background: ASCO Quality Oncology Practice Initiative (QOPI) provides tools for oncology practices to assess quality and adherence to clinical guidelines. Following each data submission a QOPI measures summary report is published providing practices the opportunity to compare themselves to QOPI Aggregates. In 2011, QOPI initiated a more stringent evaluation of family history documentation, which would improve rates of referral to genetic counseling for breast and colon cancer. METHODS A review of QOPI measure summary reports is performed by Rhode Island Hospitals (RIH) Comprehensive Cancer Center Quality Improvement Team after each round of chart abstraction. Following review of QOPI practice results for genetic evaluation in 2011, our interventions included development and implementation of a 3 generation maternal and paternal family history intake form, genetics referral form with criteria to refer patients for genetic evaluation and initiation of a Genetics Clinic on site at the Cancer Center. RESULTS Presented is a summary of QOPI results for the Breast Cancer measures of complete family history documented and Genetic testing addressed appropriately. CONCLUSIONS Our interventions included a patient intake form, genetics referral form with criteria to refer patients and a Genetics Clinic on site at the Cancer Center. The institution of a patient intake form resulted in a 19-fold improvement in complete family history documentation. The genetics referral form and establishment of an on-site Genetics clinic resulted in a 10% increase in referrals for genetic risk assessment. In spite of these interventions review of our Genetic Risk Evaluation data is notable for a 39% no show rate for the genetic risk assessment appointments. [Table: see text].

Quality improvement outcomes in an academic practice participating in ASCO’s Quality Oncology Practice Initiative (QOPI).

206 Background: The ASCO QOPI is an instrument for community and academic practices to assess quality and adherence to guidelines in areas of treatment planning and goals, chemotherapy consent documentation, smoking cessation, symptom control, palliative care, and disease specific measures. Following data submission QOPI summary reports for the submitting practice and QOPI aggregate are available for review and comparison. METHODS The academic practice of Rhode Island Hospital Comprehensive Cancer Center has participated in QOPI since the fall of 2008. QOPI measure summary reports for our practice and comparison to the Academic Aggregate are reviewed by our physicians after each round of chart abstraction, measures are identified for improvement. Interventions include education on practice improvement and development of policy and procedures for implementation by our Quality Control Officer in compliance with hospital policies. RESULTS Presented is a summary of quality improvement interventions implemented. Additional areas of quality improvement have been identified based on QOPI data, and improvement plans are ongoing including treatment summaries for patient and primary care physicians, tools to assess patient emotional well being, documentation of family history and referral for genetic assessment. CONCLUSIONS QOPI provides a platform for collection, analysis and comparison of quality measures. For the measures of formulating a pain plan the intervention was a reminder to document the plan. For the measure hospice enrollment, a reflection on our hospice enrollment has lead to an increase in referral to palliative care. The ASCO QOPI program is a tool for quality improvement, our Quality Control Officer was essential in implementation of our improvement projects. [Table: see text].