RC0639: phase II study of paclitaxel, trastuzumab, and lapatinib as adjuvant therapy for early stage HER2-positive breast cancer.

Lapatinib adds to the efficacy of trastuzumab in preclinical models and also in the neo-adjuvant setting. This study assesses the safety and feasibility of adding lapatinib to paclitaxel and trastuzumab (THL) as part of the adjuvant therapy for HER2-positive breast cancer (HER2+ BC). In this single-arm phase II study, patients with stages I-III HER2+ BC received standard anthracycline-based chemotherapy followed by weekly taxane, with concurrent standard trastuzumab, plus daily lapatinib for a total of 12 months. The primary endpoint was symptomatic congestive heart failure, secondary endpoints included overall safety. A total of 109 eligible patients were enrolled. Median follow-up is 4.3 years. No patients experienced congestive heart failure while on treatment. Mean left ventricular ejection fraction at baseline and at the end of THL were 63.6 % (N = 109, SD = 5.7) and 59.8 % (N = 98, SD = 8.1), respectively [mean change -3.95 % (N = 98, SD = 8.3), p < 0.001]. One hundred and two patients initiated post-AC treatment; of them, 31 % experienced grade 3 (no G4) diarrhea with lapatinib at 750 mg/day. The addition of lapatinib to paclitaxel and trastuzumab following AC does not add cardiac toxicity. Lapatinib dose of 750 mg/day in combination with standard chemotherapy plus trastuzumab has acceptable overall tolerability.

Prognosis and outcome of small (<=1 cm), node-negative breast cancer on the basis of hormonal and HER-2 status.

Long-term outcomes and hence the role of adjuvant therapy in patients with small (≤1 cm), node-negative breast cancer remain unclear. This study's objective was to evaluate whether human epidermal growth factor receptor (HER)-2 status is an independent, poor prognostic marker in patients with these tumors and to identify a subgroup of patients with these small tumors who might benefit from adjuvant systemic therapy. All patients with a diagnosis of a node-negative breast tumor measuring ≤1 cm and available HER-2 test results between January 1, 2001, and December 31, 2005, at the three Mayo Clinic sites were identified. Clinicopathologic data were compared in three groups: HER-2(-), HER-2(+), and triple-negative (TN) tumors. Of the 421 tumors identified, 364 (86.5%) were HER-2(-), 28 (6.7%) were HER-2(+), and 29 (6.9%) were TN. The median follow-up time was 1,015 days (range, 1-2,549 days). Groups were balanced in terms of patient age and tumor histology. Eleven patients with HER-2(-) tumors (3.0%), seven with HER-2(+) tumors (25.0%), and eight with TN tumors (27.6%) received adjuvant chemotherapy. Follow-up data were available for 357, 28, and 28 patients in the three groups, respectively. Death rates in the three groups were 6.4% (23 of 357) (one recurrence-related death), 0% (0 of 28), and 7.1% (2 of 28) (one recurrence-related death), respectively. During follow-up, the tumor recurred in nine patients: four were HER-2(-) tumors (1.1%), two were HER-2(+) tumors (7.1%), and three were TN tumors (10.7%). Patients with small, node-negative breast tumors have an excellent prognosis, but HER-2(+) and TN tumors appear to have a higher recurrence rate, warranting consideration for broad use and optimization of systemic adjuvant treatments.

Managing high-risk breast cancer.

OBJECTIVES: To identify breast cancer patients at high risk for recurrence. To describe current evidence for clinical management of early and locally advanced breast cancer and integrate this knowledge into nursing practice. DATA SOURCES: Articles, abstracts, and practice guidelines. CONCLUSION: Recent clinical trials have integrated the biology of breast cancer into individualized systemic therapy. Risk-adjusted treatment is driven by the addition of taxane therapy to systemic therapy, aromatase inhibitors, and trastuzumab into adjuvant therapy strategies. IMPLICATIONS FOR NURSING PRACTICE: The decision to initiate systemic adjuvant therapy requires knowledge of risk of relapse, integration of evidence from clinical trials, and facilitation of patient decision-making.

Challenges of oral medications in patients with advanced breast cancer.

OBJECTIVES: To list methods that nurses can use to monitor and ensure compliance with an oral agent for the treatment of metastatic breast cancer. DATA SOURCES: Published research articles, abstracts, and clinical experience. CONCLUSION: Oral chemotherapeutic agents offer the advantages of patient control and less interference with administration and, frequently, improved tolerability profiles versus conventional infusion chemotherapy. However, there is the difficulty of ensuring optimal adherence to the treatment plan. Adherence rates for oral chemotherapy vary widely in studies, and can depend on psychological and socioeconomic factors as well as individual patient outcome expectations. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses can identify factors influencing adherence to therapy and assess those patients appropriate for oral therapy. Oncology nurses can facilitate follow-up visits, ask appropriate adherence questions, and successfully manage the shift of administration responsibility to the patient.

Anthracycline vs nonanthracycline adjuvant therapy for breast cancer.

The treatment of breast cancer has progressed substantially over the past 15 years. Data from randomized adjuvant trials have shown that the risk of disease recurrence and death is significantly reduced when adjuvant chemotherapy and/or hormonal therapy is added to treatment. As new strategies are incorporated, one of the continued controversies in patient management is whether adjuvant anthracyclines should be the preferred treatment for all patients. Data from randomized and translational clinical trials have become available and are helping to elucidate the proper role of anthracyclines, as well as their acute and long-term toxicities. In most situations, an anthracycline is currently preferred, but other single and combination chemotherapies are currently under evaluation and appear promising for use in the adjuvant setting. Continued breast cancer research using molecular markers (such as topoisomerase II-alpha and gene clusters) as predictors of treatment response, could help individualize decisions regarding whether to incorporate anthracyclines into adjuvant therapy regimens.

Recent advances in adjuvant therapy for breast cancer.

OBJECTIVES: To review recent studies that may influence the adjuvant treatment of patients with breast cancer. Studies reviewed evaluate the role of aromatase inhibitors, incorporation of taxanes into chemotherapy regimens, novel dosage schedules, and supportive care with epoetin alfa. DATA SOURCES: Published literature and clinical experience. CONCLUSION: Recent evidence suggests that aromatase inhibitors are more effective than tamoxifen as hormonal adjuvant therapy and that the addition of taxanes to adjuvant chemotherapy improves outcome. Supportive care is also an important component of therapy. IMPLICATIONS FOR NURSING PRACTICE: Knowledge of recent advances in adjuvant therapy for breast cancer will contribute to greater efficacy in patient care.

Lapatinib side-effect management.

Lapatinib is an oral dual tyrosine kinase inhibitor targeting epidermal growth factor receptor and HER2. Diarrhea and dermatologic adverse events are reported commonly by patients treated with lapatinib. Diarrhea can range from mild to severe based on the agents used in combination with lapatinib. The adverse events may diminish quality of life, reduce treatment adherence, and lead to discontinuation of therapy. Consequently, proactive management of diarrhea is crucial, especially in patients receiving lapatinib in combination with other agents that also cause diarrhea. As the utility of lapatinib expands, crucial proactive diarrhea-management and dose-reduction strategies are evolving to decrease the likelihood of grade 3 or 4 toxicity. With regard to dermatologic adverse events, most are mild to moderate in severity, are of limited duration, and frequently do not require treatment intervention. However, in some patients, management of dermatologic adverse events is of great importance. This article reviews data regarding diarrhea and dermatologic adverse events in patients treated with lapatinib and summarizes the key role that oncology nurses play in educating patients about the potential for adverse events and the importance of preventive measures, ongoing surveillance, appropriate treatment, and dose reductions.

Adjuvant trastuzumab for HER2-positive early breast cancer.

This article reviews clinical data on adjuvant trastuzumab (Herceptin, Genentech, Inc.) for patients with HER2-positive early breast cancer. Published articles were searched via PubMed (1985-2009), and abstracts were located from meeting books or search engines of congress Web sites (1994-2009). Search terms included breast neoplasms, breast cancer, breast tumor, or breast tumour and adjuvant plus HER2-positive plus trastuzumab. Trastuzumab improves clinical outcomes as well as disease-free and overall survival for patients with early HER2-positive breast cancer compared with adjuvant chemotherapy alone in this population. Trastuzumab has a favorable safety profile; levels of cardiac dysfunction were acceptable in all adjuvant trials, and cardiac dysfunction was manageable in most cases. Awareness of the clinical data will help nurses identify patients eligible for adjuvant trastuzumab, familiarize them with treatment and cardiac monitoring plans, and provide them with information to help advise, treat, and support patients from diagnosis through completion of therapy.

Comprehensive diagnostic program for medically underserved women with abnormal breast screening evaluations in an urban population.

OBJECTIVE: To institute a patient navigator program for underinsured women to eliminate delays in diagnostic resolution of abnormal screening mammograms, provide services for abnormalities noted during breast cancer screening, describe demographic and clinical characteristics of enrollees, and assess postscreening follow-up care. PATIENTS AND METHODS: Coordinators from area health departments worked with a navigator nurse at Mayo Clinic Cancer Center in Jacksonville, FL, to refer patients for additional diagnostic services, including diagnostic mammography, ultrasonography, ultrasonography-guided biopsy, stereotactic biopsy, breast magnetic resonance imaging, and biopsy guided by magnetic resonance imaging. Women with abnormal screening mammograms (Breast Imaging Reporting and Data System [BI-RADS] category 4 or 5) or palpable suspect breast masses were eligible. Data were extracted from clinical service records. Timeliness of postscreening follow-up was assessed. RESULTS: The study enrolled 447 women from June 30, 2000, to December 29, 2006. Data on the time from screening to diagnosis were available for 399 women, and median time from detection of screening abnormality to diagnosis was 37 days. Time between screening and diagnosis was 60 days or less for 325 (81%) of the 399 women for whom data were available and for 60 (82%) of the 73 women with BI-RADS category 4 or 5 assessments. Both of these percentages exceeded the Centers for Disease Control and Prevention quality benchmark of 75%. Mean time from study enrollment to diagnosis was 2 days for women with BI-RADS category 3 or 4 assessments and 7 days for women with BI-RADS category 5 assessments. CONCLUSION: This program demonstrated a successful collaboration between an academic medical center and community health centers. Most women with BI-RADS category 4 or 5 assessments received a diagnosis within 60 days of screening.

Weekly administration of docetaxel and paclitaxel in metastatic or advanced breast cancer.

The taxanes docetaxel (Taxotere; Aventis Pharmaceuticals Inc., Bridgewater, NJ, http://www.aventispharma-us.com) and paclitaxel (Taxol; Bristol-Myers Squibb, Princeton, NJ, http://www.bms.com) have significant clinical activity in metastatic breast cancer. A number of clinical trials have evaluated the tolerability and efficacy of weekly taxane administration to optimize the benefit-to-risk ratio in metastatic breast cancer. Single-agent studies with docetaxel and paclitaxel in metastatic breast cancer show clinically significant antitumor activity even in advanced, heavily pretreated, resistant, and/or refractory disease. This activity is also evident with taxane-based combination regimens. Severe hematologic and nonhematologic toxicities are infrequent, with other toxicities noted based on the dose and weekly regimen selected. Weekly docetaxel and paclitaxel regimens represent valuable therapeutic options for women with metastatic breast cancer and have entered evaluation as part of adjuvant therapy for this disease.

Adjuvant therapy for breast cancer: recommendations for management based on consensus review and recent clinical trials.

Determining the optimal individual adjuvant systemic therapy for breast cancer patients is a challenging undertaking because it requires translating data from clinical trials that have involved thousands of patients into a highly individualized, risk-adjusted approach for the patient at hand. Choosing adjuvant therapy for women with breast cancer includes consideration of four issues: A) evaluation of risk of relapse; B) extrapolation of results from clinical trials; C) therapeutic ratio, and D) the patient's preferences following a thorough discussion with her physician. Data from recently completed phase III adjuvant trials and worldwide consensus conferences document the benefits of adjuvant therapy in improving disease-free survival and overall survival for patients diagnosed with invasive breast cancer >1.0 cm in size. The benefits of hormonal therapy are clear, but limited to patients with estrogen receptor-positive breast cancer. Anthracyclines lead to improved outcomes compared with nonanthracycline regimens. Taxanes appear to improve disease-free survival in patients with node-positive disease, although longer follow-up is required to assess their impact on overall survival. Some countries have reported a reduction in the mortality rate from breast cancer over the past several years. The improved survival rate is due, at least in part, to the use of adjuvant systemic therapy. Ongoing studies are evaluating targeted therapies, with the potential of remarkably improving patient outcome.