Tamoxifen significantly reduces tumor recurrence in certain patients with early-stage estrogen receptor-positive breast cancer, but markers predictive of treatment failure have not been identified. Here, we generated gene expression profiles of hormone receptor-positive primary breast cancers in a set of 60 patients treated with adjuvant tamoxifen monotherapy. An expression signature predictive of disease-free survival was reduced to a two-gene ratio, HOXB13 versus IL17BR, which outperformed existing biomarkers. Ectopic expression of HOXB13 in MCF10A breast epithelial cells enhances motility and invasion in vitro, and its expression is increased in both preinvasive and invasive primary breast cancer. The HOXB13:IL17BR expression ratio may be useful for identifying patients appropriate for alternative therapeutic regimens in early-stage breast cancer.

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Purpose: Most node-negative breast cancer patients are older and postmenopausal and are increasingly being offered adjuvant chemotherapy despite their low overall risk of distant relapse. A molecular diagnostic test with high negative predictive value (NPV) for distant metastasis in this subgroup would spare many older breast cancer patients adjuvant treatment. Experimental Design:We determined the NPVand positive predictive value of the MammaPrint assay in breast cancer patients who were consecutively diagnosed and treated at the Massachusetts General Hospital between 1985 and 1997. Primary tumors from 100 patients with nodenegative, invasive breast cancer (median age, 62.5 years; median follow-up, 11.3 years) were subjected to MammaPrint analysis and classified as being at either low or high risk for distant metastasis.Results: The MammaPrint 70-gene signature displayed excellent NPV as in previous studies, correctly identifying 100% of women at low risk for distant metastases at 5 years. However, this assay had a lower positive predictive value (12% at 5 years) than previously observed. Conclusions: The MammaPrint assay was originally designed to identify younger breast cancer patients at low risk for distant metastasis, who might consequently be spared systemic treatment. We show here that the same signature has a very high NPV for distant recurrence after adjuvant treatment in older breast cancer patients.

Summary The Survivor’s Health and Reaction (SHARE) study used a quality of life model adapted for cancer survivors by Dow, Ferrell and colleagues to identify factors related to global health-related quality of life (HRQL) and the prevalence of problems and healthy behaviors in breast cancer patients who participated in CALGB 8541. A total of 245 survivors (78% of those invited) who were 9.4 to 16.5 years post-diagnosis completed surveys that inquired about current HRQL, economic, spiritual, physical and psychosocial concerns, and health behaviors, (e.g. smoking, exercise, and supplement use). A regression model developed to characterize global self-assessment of HRQL from all domains showed a negative effect on global HRQL from lower social support (OR=1.03, 95% CI: 1.02, 1.05), having heart disease (OR=5.01, 95% CI: 1.39, 18.1), decreased energy (OR=1.05, 95% CI: 1.03, 1.07), and having 2 or more co-morbidities (OR=2.39, 95%CI: 1.10,5.19). Some women reported engaging in healthy behaviors since their cancer diagnosis, such as increasing exercise (31%), and reducing/quitting smoking (20%). The most prevalent problem reported was menopausal symptoms (59%). Although breast cancer survivors reported making positive lifestyle changes, physical and social factors, such as heart disease, decreased social support and having 2 or more comorbidities were found to be significantly related to HRQL. Factors related to psychological, spiritual and economic domains were not predictive of global HRQL. Suggestions are provided for areas in which to target interventions in order to improve HRQL in long-term breast cancer survivors.