National Comprehensive Cancer Network

NCCN Guidelines^® & Clinical Resources

JNCCN – The Journal of the National Comprehensive Cancer Network

Table of Contents - Volume 7 Number 2: February 2009

• NCCN Clinical Practice Guidelines in Oncology™
• Breast Cancer
• Special Feature:
• Predictors and Temporal Trends of Adjuvant Aromatase Inhibitor Use in Breast Cancer
• Featured Articles
• Indications for Breast MRI in the Patient with Newly Diagnosed Breast Cancer
• Pharmacogenetics of Tamoxifen: Who Should Undergo CYP2D6 Genetic Testing?
• APBI – Where Do We Stand?
• Geriatric Assessment in Older Patients with Breast Cancer

NCCN Clinical Practice Guidelines in Oncology™

Breast Cancer

The American Cancer Society estimates that 184,450 new cases of invasive breast cancer will be diagnosed and 40,930 patients will die of the disease in the United States in 2008. In addition, approximately 67,770 women will be diagnosed with carcinoma in situ of the breast. Breast cancer is the most common malignancy in women in the United States and is second only to lung cancer as a cause of cancer death. The incidence of breast cancer has increased steadily in the United States over the past few decades, but breast cancer mortality seems to be declining, suggesting a benefit from early detection and more effective treatment. These guidelines discuss diagnosis, treatment, and follow-up for invasive breast cancer.

Special Feature

Predictors and Temporal Trends of Adjuvant Aromatase Inhibitor Use in Breast Cancer
Tiffany H. Svahn, MD; Joyce C. Niland, PhD; Robert W. Carlson, MD; Melissa E. Hughes, MSc; Rebecca A. Ottesen, MS Richard L. Theriault, DO; Stephen B. Edge, MD; Anne F. Schott, MD; Michael A. Bookman, MD; and Jane C. Weeks, MD

This study examines adjuvant endocrine therapy in postmenopausal women following the first report of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial, identifies temporal relationships in aromatase inhibitor use, and examines characteristics associated with choice of endocrine therapy. This study examined 4044 postmenopausal patients presenting with hormone receptor–positive nonmetastatic breast cancer from July 1997 to December 2003. Multivariable logistic regression analysis examined temporal associations and characteristics associated with aromatase inhibitor use. Time-trend analysis showed increased aromatase inhibitor and decreased tamoxifen use after release of ATAC results. In multivariable regression analysis, institution, vascular disease, age, stage, and HER2 status independently predicted aromatase inhibitor use. Institutional rates of use ranged from 15% to 66%. Adjuvant aromatase inhibitor use increased after the first report of ATAC, with this increase associated with older age, vascular disease, overexpression of HER2, or more advanced stage. Substantial variation was seen among institutions.

Featured Articles

Indications for Breast MRI in the Patient with Newly Diagnosed Breast Cancer
Constance D. Lehman, MD, PhD; Wendy DeMartini, MD; Benjamin O. Anderson, MD; and Stephen B. Edge MD

Use of breast MRI in the preoperative evaluation of patients recently diagnosed with breast cancer has increased significantly over the past 10 years because of its well-documented high sensitivity for detecting otherwise occult breast cancer in the affected and contralateral breasts. However, published research reports on the impact of this improved cancer detection are limited. Equally important are growing concerns that the quality of breast MRI may vary significantly across practice sites, and therefore the published value of MRI may not be achieved for many patients. This article describes the peer-reviewed, published clinical research trials evaluating breast MRI in patients with newly diagnosed breast cancer on which the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology are based, and provides recommendations for the performance of high-quality breast MRI and suggestions for future research.

Pharmacogenetics of Tamoxifen: Who Should Undergo CYP2D6 Genetic Testing?
Michaela J. Higgins, MRCPI; James M. Rae, PhD; David A. Flockhart, MD, PhD; Daniel F. Hayes, MD; and Vered Stearns, MD

Many women with hormone receptor–positive breast cancer will receive tamoxifen at some point in their treatment course. Tamoxifen is biotransformed to the potent antiestrogen endoxifen almost exclusively through the cytochrome P450 (CYP) 2D6 isoform. Although prospective data are lacking, the balance of evidence available currently suggests that a single nucleotide polymorphism in the CYP2D6 gene, particularly the presence of 2 null alleles, predicts for reduced tamoxifen metabolism and possibly poorer outcome than expected in patients with a wild-type genotype. Until data are available from retrospective examinations of the large prospective trials already conducted, or adequately powered prospective analyses, transforming this information into guidelines for individual patients remains challenging. Ongoing research is directed toward identifying other polymorphisms that may influence the efficacy and safety of tamoxifen, other hormonal agents, and chemotherapies used to treat breast cancer. The hope is that in the future, not only tumor-associated factors but also germ-line host genetics can be used to determine whether a woman should undergo treatment, and with which specific agents, to prevent breast cancer recurrence or death or avoid drug-related toxicities.

APBI – Where Do We Stand?
Frederick M. Dirbas, MD

Accelerated partial breast irradiation given (APBI) over 1 to 5 days is a new form of post-lumpectomy radiotherapy that could provide a safe, effective replacement for whole breast radiotherapy. Early trials showed high local recurrence rates, but more recent single and multi-institutional studies have demonstrated recurrence rates comparable to whole breast radiotherapy. There are currently 4 major approaches to APBI, each with significant nuances. Seven phase III studies are now in progress comparing various forms of APBI with whole breast radiotherapy. This review presents a method for evaluating different patient cohorts and APBI techniques, recent developments with APBI in phase I and II studies are summarized, and differences among phase III studies in progress are highlighted.

Geriatric Assessment in Older Patients with Breast Cancer
Heidi Klepin, MD; Supriya Mohile, MD; and Arti Hurria, MD

Most cases of breast cancer are diagnosed in older adults; older women have an increased risk for breast cancer–specific mortality and are at higher risk for treatment-associated morbidity than younger women. However, they are less likely to be offered preventive care or adjuvant therapy. Major gaps in evidence exist regarding the optimal evaluation and treatment of older women with breast cancer, because of significant underrepresentation in clinical trials. Chronologic age alone is an inadequate predictor of treatment tolerance and benefit in this heterogeneous population. Multiple issues uniquely associated with aging impact cancer care, including functional impairment, comorbidity, social support, cognitive function, psychological state, and financial stress. Applying geriatric principles and assessment to this older adult population would inform decision making by providing estimates of life expectancy and identifying individuals most vulnerable to morbidity. Ongoing research is seeking to identify which assessment tools can best predict outcomes in this population, and thus guide experts in tailoring treatments to maximize benefits in older adults with breast cancer.