RCB determined from routine pathologic materials represented the distribution of RD, was a significant predictor of DRFS, and can be used to define categories of near-complete response and chemotherapy resistance.

A B S T R A C T PurposeTo evaluate the risk of recurrence in women diagnosed with T1a and T1b, node-negative, human epidermal growth factor receptor 2 (HER2) -positive breast cancer. MethodsWe reviewed 965 T1a,bN0M0 breast cancers diagnosed at our institution between 1990 and 2002. Dedicated breast pathologists confirmed HER2 positivity if 3ϩ by immunohistochemistry or if it had a ratio of 2.0 or greater by fluorescence in situ hybridization (FISH). Patients who received adjuvant chemotherapy or trastuzumab were excluded. Kaplan-Meier product was used to calculate recurrence-free survival (RFS) and distant recurrence-free survival (DRFS). Cox proportional hazard models were fit to determine associations between HER2 status and survival after adjustment for patient and disease characteristics. Additionally, 350 breast cancers from two other institutions were used for validation. ResultsTen percent of patients had HER2-positive tumors. At a median follow-up of 74 months, there were 72 recurrences. The 5-year RFS rates were 77.1% and 93.7% in patients with HER2-positive and HER2-negative tumors, respectively (P Ͻ .001). The 5-year DRFS rates were 86.4% and 97.2% in patients with HER2-positive and HER2-negative tumors, respectively (P Ͻ .001). In multivariate analysis, patients with HER2-positive tumors had higher risks of recurrence (hazard ratio [HR], 2.68; 95% CI, 1.44 to 5.0; P ϭ .002) and distant recurrence (HR, 5.3; 95% CI, 2.23 to 12.62; P Ͻ .001) than those with HER2-negative tumors. Patients with HER2-positive tumors had 5.09 times (95% CI, 2.56 to 10.14; P Ͻ .0001) the rate of recurrences and 7.81 times (95% CI, 3.17 to 19.22; P Ͻ .0001) the rate of distant recurrences at 5 years compared with patients who had hormone receptor-positive tumors. ConclusionPatients with HER2-positive T1abN0M0 tumors have a significant risk of relapse and should be considered for systemic, anti-HER2, adjuvant therapy.

Purpose We hypothesize that measurement of gene expression related to estrogen receptor α (ER; gene name ESR1) within a breast cancer sample represents intrinsic tumoral sensitivity to adjuvant endocrine therapy. Methods A genomic index for sensitivity to endocrine therapy (SET) index was defined from genes coexpressed with ESR1 in 437 microarray profiles from newly diagnosed breast cancer, unrelated to treatment or outcome. The association of SET index and ESR1 levels with distant relapse risk was evaluated from microarrays of ER-positive breast cancer in two cohorts who received 5 years of tamoxifen alone as adjuvant endocrine therapy (n = 225 and 298, respectively), a cohort who received neoadjuvant chemotherapy followed by tamoxifen and/or aromatase inhibition (n = 122), and two cohorts who received no adjuvant systemic therapy (n = 208 and 133, respectively). Results The SET index (165 genes) was significantly associated with distant relapse or death risk in both tamoxifen-treated cohorts (hazard ratio [HR] = 0.70, 95% CI, 0.56 to 0.88, P = .002; and HR = 0.76, 95% CI, 0.63 to 0.93, P = .007) and in the chemo-endocrine–treated cohort (HR = 0.19; 95% CI, 0.05 to 0.69, P = .011) independently from pathologic response to chemotherapy, but was not prognostic in two untreated cohorts. No distant relapse or death was observed after tamoxifen alone if node-negative and high SET or after chemo-endocrine therapy if intermediate or high SET. Conclusion The SET index of ER-related transcription predicted survival benefit from adjuvant endocrine therapy, not inherent prognosis. Prior chemotherapy seemed to enhance the efficacy of adjuvant endocrine therapy related to SET index.