Original StudyEvaluation of Prognosis in Hormone Receptor–Positive/HER2-Negative and Lymph Node–Negative Breast Cancer With Low Oncotype DX Recurrence Score
Introduction
Breast cancer is the most common cancer in women worldwide and in the United States; approximately 1 (12%) in 8 US women will develop invasive breast cancer over the course of a lifetime. In 2017, an estimated 252,710 new cases of invasive breast cancer are expected to be diagnosed in women in the United States.1 Breast cancer mortality rates, however, have been decreasing since the 1970s, partially as a result of improved breast cancer screening and improvements in systemic therapy.2, 3, 4 Breast cancer is no longer regarded as a single disease.5 Clinically, breast cancers are subclassified by estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) gene amplification. Different subtypes have different tumor biology that affects prognosis and response to therapies.6, 7, 8, 9, 10, 11, 12 Hormone receptor (HR)-positive (ER+ and/or PR+) and HER2-negative breast cancers generally have a good prognosis.13, 14, 15, 16, 17, 18, 19, 20
Approximately 70% to 80% of breast cancers are ER and/or PR positive, and almost all of these patients will receive endocrine therapy for at least 5 years as part of the standard of care. Not all of these patients need chemotherapy, however, particularly when diagnosed at an early disease stage, and overtreatment with chemotherapy is important to avoid because chemotherapy can have significant short-term and long-term toxicities. For patients with HR-positive/HER2-negative, lymph node (LN)-negative cancers, a 21-gene expression assay (Oncotype DX; ODX) can provide additional prognostic information and can be predictive of benefit from adjuvant chemotherapy independent of clinicopathologic features such as tumor grade, Ki-67 index, and lymphovascular invasion.21 Before the development and validation of this assay, treatment guidelines in the United States and Europe recommended consideration of chemotherapy for most patients.22, 23 The analysis of ODX scores in tamoxifen-treated versus tamoxifen plus chemotherapy–treated patients in the NSABP B20 trial showed that patients with an ODX score of 18 or less derived minimal, if any, benefit from chemotherapy. Since the publication of this trial and other subsequent studies, guidelines and national practice patterns have started to change.24
Several prospective studies were conducted after the initial validation of the ODX assay. In 2015, a study of 1626 women with node-negative, < 5 cm ER+ and/or PR+ breast cancers with a recurrence score of 0 to 10 who were assigned to receive endocrine therapy with no chemotherapy showed rate of invasive disease-free survival of 93.8%, rate of freedom from distant recurrence of 99.3%, and rate of overall survival (OS) of 98.0%.25 This gave further support to the notion that for the lowest-risk patients with ER+ breast cancer, chemotherapy would likely do more harm than good.
We were interested in learning more about how the other half of the low-risk ODX group, those with scores of 11 to 18, performed compared to those with scores of 0 to 10. We conducted a retrospective single-institution study evaluating patients with HR+/HER2−/LN− breast cancer who had ODX scores of 0 to 18. We compared rates of local and distant disease-free survival and OS between patients with scores 0 to 10 and those with scores 11 to 18.
Section snippets
Patients and Methods
Data from a total of 332 patients with ER+/HER2−/LN− breast cancer diagnosed from 2006 to 2014 were retrieved from our institution. Among the 332 patients, 107 had an ODX score of 1 to 10 (1-10 group), and 225 had an ODX score between 11 to < 18 (11-18 group). The median follow-up of the 1-10 group was 47 months and that of the 11-18 group was 49 months. All patients received surgery. Age at diagnosis, race, ER and PR expression, HER2 immunohistochemistry evaluation (negative vs. equivocal),
Statistical Analysis
Statistical analysis was conducted by SAS 9.4 (SAS Institute, Cary, NC). For numeric covariates, means and SDs were calculated and are presented. Frequency and their percentages are shown for categoric variables. One-way ANOVA and Kruskal-Wallis tests were performed for numerical covariates and for univariate analysis if appropriate. Chi-square test or Fisher's exact test was used for categorical covariates when appropriate. The univariate association of each covariate on OS, DFS, or distant
Results
The 2 group of patients had similar age at diagnosis, race distribution, tumor size and grade, Ki-67 score, ER expression, presence of lymphovascular invasion, and tumor stage distribution (all P > .05; Table 1). All patients received surgery. Similar proportions of patients in each group received chemotherapy (5.05% in the 1-10 group, 6.05% in the 11-18 group; P = .724) and radiotherapy (52.53% in the 1-10 group, 59.07% in the 11-18 group; P = .276). The only significant difference between
Discussion
In this study, patients with an ODX score of 1 to 18 had very good prognosis. There was a trend toward more distant metastatic events and worse OS in patients with higher ODX scores. However, the small numbers of recurrences seen in this cohort makes it hard to draw definitive conclusions about differential risks between the 2 groups.
One interesting trend was that of the 8 patients who experienced recurrence (local or distant), 5 (62.5%) had either declined endocrine therapy altogether or did
Disclosure
The authors have stated that they have no conflict of interest.
Acknowledgments
Supported in part by the Biostatistics and Bioinformatics Shared Resource of Winship Cancer Institute of Emory University and National Institutes of Health (NIH)-National Cancer Institute under award P30CA138292. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
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