Adjuvant chemotherapy clearly demonstrates a reduction in mortality in breast cancer. However, the added benefit from the addition of taxanes remains uncertain. Paclitaxel and its cousin docetaxel have proven activity in the treatment of metastatic breast cancer. Toxicity has been tolerable when taxanes are used as single agents or in combination with anthracyclines. Several clinical trials are currently underway evaluating the role of taxanes in the adjuvant setting. Preliminary results from large phase III studies are promising; however, mature data are required before conclusions can be drawn. This article reviews the trials currently underway, evaluating the efficacy, dosage, scheduling, and regimens of taxanes in the adjuvant treatment of breast cancer.
Donna Trauth and Lori J. Goldstein
Lori J. Goldstein, Bonnie J. Miller, Nancy Nicotera and Delinda Pendleton
Fox Chase Cancer Center (FCCC) participated in the NCCN Opportunities for Improvement project with the purpose of optimizing the quality of care delivered at FCCC to patients with breast cancer based on the ASCO and NCCN Guidelines. Historically, FCCC’s performance has demonstrated a high level of concordance, based on findings from the NCCN Oncology Outcomes Database project benchmarking data in breast cancer. Access to the NCCN Breast Cancer Timing in Continuation and Transition of Care (TiCToC) Measures data analysis (performed by NCCN) provided an opportunity to further identify specific opportunities related to care along the continuum. The initial goal of the project was to continue participation in the NCCN Oncology Outcomes Database for Breast Cancer, with the overall objective of sustaining high concordance. FCCC’s recent data were compared with historical data and benchmarked against those from other participating NCCN Member Institutions.
Efrat Dotan, Elizabeth Handorf, Caitlin R. Meeker, Bianca Lewis, Kelly Filchner, Jennifer S. Winn and Lori J. Goldstein
Introduction: Geriatric assessment (GA) is recommended for evaluating an older cancer patient’s fitness for treatment; however, it is underutilized in the community. We sought to define the gaps that exist in community oncology practices in the assessment and management of older MBC patients through implementation and training on the use of GA for the care of older MBC patients. Methods: The first phase evaluated community oncology providers using questionnaires regarding their assessment and management of older MBC patients. The second phase included training through implementation of a patient self-administered GA among patients ≥65-years-old with MBC. The providers were blinded to the results of the GA and provided their assessment. Comparison of the 2 evaluations was conducted. The GA was ultimately shared with the providers, who were questioned about the effect of the results on care recommendations. Results: 43 providers from 10 practices were enrolled. Phase I revealed the majority (77%) of providers recognized the utility of GA, yet only 42% routinely conducted a GA pretreatment. Most providers (77%) reported evaluating various GA domains through patient interview rather than validated assessments. Validated scales were used in low rates to evaluate cognition (23%), psychosocial status (12%), and toxicity risk (9%). The limited use of validated assessment tools was not influenced by the provider’s demographics or their views of GA utility. Eighty patients took part in the training phase of the study to date, with average age 74 (range, 65–90) and 84% Caucasian. The majority of patients had subtype ER/PR+, HER2- (75%) and 46% were on first-line therapy. 277 recommended interventions were identified: 174 immediate interventions and 103 suggested interventions. Following review of these results, providers reported being surprised in 40% of the cases, mainly with lower than expected cognitive or social support scores. The providers reported plans for change in management in 44% of the patients as a result of the GA findings. Conclusion: Despite acknowledgement of the value associated with pretreatment GA, it is rarely used in the community. Furthermore, interview rather than validated assessment tools are used to identify age-related concerns. In our preliminary results, the GA identified a large number of deficient areas that had not been identified through the provider’s assessment, and resulted in management change. Additional updated results will be presented at the conference.
D. Craig Allred, Robert W. Carlson, Donald A. Berry, Harold J. Burstein, Stephen B. Edge, Lori J. Goldstein, Allen Gown, M. Elizabeth Hammond, James Dirk Iglehart, Susan Moench, Lori J. Pierce, Peter Ravdin, Stuart J. Schnitt and Antonio C. Wolff
The NCCN Task Force on Estrogen Receptor and Progesterone Receptor Testing in Breast Cancer by Immunohistochemistry was convened to critically evaluate the extent to which the presence of the estrogen receptor (ER) and progesterone receptor (PgR) biomarkers in breast cancer serve as prognostic and predictive factors in the adjuvant and metastatic settings, and the ability of immunohistochemical (IHC) detection of ER and PgR to provide an accurate assessment of the expression of these biomarkers in breast cancer tumor tissue. The task force is a multidisciplinary panel of 13 experts in breast cancer who are affiliated with NCCN member institutions and represent the disciplines of pathology, medical oncology, radiation oncology, surgical oncology, and biostatistics. The main overall conclusions of the task force are ER is a strong predictor of response to endocrine therapy; ER status of all samples of invasive breast cancer or ductal carcinoma in situ (DCIS) should be evaluated by IHC; IHC measurements of PgR, although not as important clinically as ER, can provide useful information and should also be performed on all samples of invasive breast cancer or DCIS; IHC is the main testing strategy for evaluating ER and PgR in breast cancer and priority should be given to improve the quality of IHC testing methodologies; all laboratories performing IHC assays of ER and PgR should undertake formal validation studies to show both technical and clinical validation of the assay in use; and all laboratories performing IHC assays of hormone receptors in breast cancer should follow additional quality control and assurance measures as outlined in the upcoming guidelines from the American Society of Clinical Oncology and College of American Pathologists.
Jennifer Shih, Babar Bashir, Karen S. Gustafson, Mark Andrake, Roland L. Dunbrack, Lori J. Goldstein and Yanis Boumber
Next-generation sequencing of primary and metachronous metastatic cancer lesions may impact patient care. We present a case of relapsed metastatic breast cancer with a dominant pulmonary lesion originally identified as lung adenocarcinoma. A 72-year-old, never-smoker woman with a protracted cough was found to have a large lung mass and regional lymphadenopathy on a chest CT. Lung mass biopsy showed adenocarcinoma with focal TTF-1 (thyroid transcription factor 1) positivity, favoring a lung primary. In addition to stereotactic brain radiation for cerebral metastases, she was started on carboplatin/pemetrexed. As part of the workup, the tumor was analyzed by a 50-gene targeted mutation panel, which detected 3 somatic mutations: ERBB2 (HER2) D769H activating missense mutation, TP53 Y126 inactivating truncating mutation, and SMARCB1 R374Q missense mutation. Of note, the patient had a history of stage IIA triple-negative grade 3 invasive ductal carcinoma of the left breast 1.5 years ago and received neoadjuvant chemotherapy and adjuvant radiation, and underwent a lumpectomy. Further analysis of her primary breast tumor showed a mutational profile identical to that of the lung tumor. Fluorescence in situ hybridization revealed HER2 amplification in the lung tumor, with a HER2/CEP17 ratio of 3.9. The patient was diagnosed with recurrent HER2-positive metastatic breast carcinoma with a coexisting ERBB2 (HER2) activating mutation. Chemotherapy was adjusted to include dual HER2-targeted therapy containing trastuzumab and pertuzumab, resulting in an ongoing partial response. This case demonstrates that a unique genetic mutational profile can clarify whether a tumor represents a metastatic lesion or new malignancy when conventional morphological and immunohistochemical methods are indeterminate, and can directly impact treatment decisions.
Bianca Lewis, Caitlin R. Meeker, Elizabeth Handorf, Kelly Filchner, Rino Seedor, Jennifer S. Winn, Lori J. Goldstein and Efrat Dotan
Robert W. Carlson, Susan Moench, Arti Hurria, Lodovico Balducci, Harold J. Burstein, Lori J. Goldstein, William J. Gradishar, Kevin S. Hughes, Mohammad Jahanzeb, Stuart M. Lichtman, Lawrence B. Marks, Joan S. McClure, Beryl McCormick, Lisle M. Nabell, Lori J. Pierce, Mary Lou Smith, Neal S. Topham, Tiffany A. Traina, John H. Ward and Eric P. Winer
Breast cancer is common in older women, and the segment of the U.S. population aged 65 years and older is growing rapidly. Consequently, awareness is increasing of the need to identify breast cancer treatment recommendations to assure optimal, individualized treatment of older women with breast cancer. However, the development of these recommendations is limited by the heterogeneous nature of this population with respect to functional status, social support, life expectancy, and the presence of comorbidities, and by the underrepresentation of older patients with breast cancer in randomized clinical trials. The NCCN Breast Cancer in the Older Woman Task Force was convened to provide a forum for framing relevant questions on topics that impact older women with early-stage, locally advanced, and metastatic breast cancer. The task force is a multidisciplinary panel of 18 experts in breast cancer representing medical oncology, radiation oncology, surgical oncology, geriatric oncology, geriatrics, plastic surgery, and patient advocacy. All task force members were from NCCN institutions and were identified and invited solely by NCCN. Members were charged with identifying evidence relevant to their specific expertise. During a 2-day meeting, individual members provided didactic presentations; these presentations were followed by extensive discussions during which areas of consensus and controversy were identified on topics such as defining the “older” breast cancer patient; geriatric assessment tools in the oncology setting; attitudes of older patients with breast cancer and their physicians; tumor biology in older versus younger women with breast cancer; implementation of specific interventions in older patients with breast cancer, such as curative surgery, surgical axillary staging, radiation therapy, reconstructive surgery, endocrine therapy, chemotherapy, HER2-directed therapy, and supportive therapies; and areas requiring future studies. (JNCCN 2008;6[Suppl 4]:S1–S25)
Margaret A. O'Grady, Elena Gitelson, Ramona F. Swaby, Lori J. Goldstein, Elaine Sein, Patricia Keeley, Bonnie Miller, Tianyu Li, Alan Weinstein and Steven J. Cohen
Fox Chase Cancer Center Partners (FCCCP) is a community hospital/academic partnership consisting of 25 hospitals in the Delaware Valley. Originally created in 1986, FCCCP promotes quality community cancer care through education, quality assurance, and access to clinical trial research. An important aspect of quality assurance is a yearly medical oncology audit that benchmarks quality indicators and guidelines and provides a roadmap for quality improvement initiatives in the community oncology clinical office setting. Each year, the FCCCP team and the Partner Medical Oncologists build disease site- and stage-specific indicators based on National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology. Concordance with multiple indicators is assessed on 20 charts from each community practice. A report for each FCCCP medical oncology practice summarizes documentation, screening recommendations, new drug use, and research trends in a particular disease site. Descriptive statistics reflect indicators met, number of new cases seen per year, number of disease site cases from tumor registry information, and clinical trial accrual total. Education and documentation tools are provided to physicians and oncology office nursing staff. The FCCCP Clinical Operations Team, consisting of medical oncologists and oncology-certified nurses, has conducted quality audits in medical oncology offices for 7 years using NCCN-derived indicators. Successful audits comprising gastric, colorectal, and breast cancer have been the focus of recent evaluations. For the 2005 stage II/III breast cancer evaluation, mean compliance per parameter was 88%, with 15 of 16 practices achieving mean compliance greater than 80%. A large-scale quality assurance audit in a community cancer partner network is feasible. Recent evaluation of localized breast cancer shows high compliance with guidelines and identifies areas for focused education. Partnership between academic and community oncologists produces a quality review process that is broadly applicable and adaptable to changing medical knowledge.
Robert W. Carlson, Susan J. Moench, M. Elizabeth H. Hammond, Edith A. Perez, Harold J. Burstein, D. Craig Allred, Charles L. Vogel, Lori J. Goldstein, George Somlo, William J. Gradishar, Clifford A. Hudis, Mohammad Jahanzeb, Azadeh Stark, Antonio C. Wolff, Michael F. Press, Eric P. Winer, Soonmyung Paik, Britt-Marie Ljung and for the NCCN HER2 Testing in Breast Cancer Task Force
The NCCN HER2 Testing in Breast Cancer Task Force was convened to critically evaluate the ability of the level of HER2 expression or gene amplification in breast cancer tumors to serve as a prognostic and a predictive factor in the metastatic and adjuvant settings, to assess the reliability of the methods of measuring HER2 expression or gene amplification in the laboratory, and to make recommendations regarding the interpretation of test results. The Task Force is a multidisciplinary panel of 24 experts in breast cancer representing the disciplines of medical oncology, pathology, radiation oncology, surgical oncology, epidemiology, and patient advocacy. Invited members included members of the NCCN Breast Cancer Panel and other needed experts selected solely by the NCCN. During a 2-day meeting, individual task force members provided didactic presentations critically evaluating important aspects of HER2 biology and epidemiology: HER2 as a prognostic and predictive factor; results from clinical trials in which trastuzumab was used as a targeted therapy against HER2 in the adjuvant and metastatic settings; the available testing methodologies for HER2, including sensitivity, specificity, and ability to provide prognostic and predictive information; and the principles on which HER2 testing should be based. Each task force member was charged with identifying evidence relevant to their specific expertise and presentation. Following the presentations, an evidence-based consensus approach was used to formulate recommendations relating to the pathologic and clinical application of the evidence to breast cancer patient evaluation and care. In areas of controversy, this process extended beyond the meeting to achieve consensus. The Task Force concluded that accurate assignment of the HER2 status of invasive breast cancer is essential to clinical decision making in the treatment of breast cancer in both adjuvant and metastatic settings. Formal validation and concordance testing should be performed and reported by laboratories performing HER2 testing for clinical purposes. If appropriate quality control/ assurance procedures are in place, either immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) methods may be used. A tumor with an IHC score of 0 or1+, an average HER2 gene/chromosome 17 ratio of less than 1.8, or an average number of HER2 gene copies/cell of 4 or less as determined by FISH is considered to be HER2 negative. A tumor with an IHC score of 3+, an average HER2 gene/chromosome 17 ratio of greater than 2.2 by FISH, or an average number of HER2 gene copies/cell of 6 or greater is considered HER2 positive. A tumor with an IHC score of 2+ should be further tested using FISH, with HER2 status determined by the FISH result. Tumor samples with an average HER2 gene/chromosome ratio of 1.8 to 2.2 or average number of HER2 gene copies/cell in the range of greater than 4 to less than 6 are considered to be borderline, and strategies to assign the HER2 status of such samples are proposed. (JNCCN 2006;4(Suppl 3):S1–S22)