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Purpose To determine the pathologic complete response (pCR) rate in estrogen receptor (ER) -positive primary breast cancer triaged to chemotherapy when the protein encoded by the MKI67 gene (Ki67) level was > 10% after 2 to 4 weeks of neoadjuvant aromatase inhibitor (AI) therapy. A second objective was to examine risk of relapse using the Ki67-based Preoperative Endocrine Prognostic Index (PEPI). Methods The American College of Surgeons Oncology Group (ACOSOG) Z1031A trial enrolled postmenopausal women with stage II or III ER-positive (Allred score, 6 to 8) breast cancer whose treatment was randomly assigned to neoadjuvant AI therapy with anastrozole, exemestane, or letrozole. For the trial ACOSOG Z1031B, the protocol was amended to include a tumor Ki67 determination after 2 to 4 weeks of AI. If the Ki67 was > 10%, patients were switched to neoadjuvant chemotherapy. A pCR rate of > 20% was the predefined efficacy threshold. In patients who completed neoadjuvant AI, stratified Cox modeling was used to assess whether time to recurrence differed by PEPI = 0 score (T1 or T2, N0, Ki67 < 2.7%, ER Allred > 2) versus PEPI > 0 disease. Results Only two of the 35 patients in ACOSOG Z1031B who were switched to neoadjuvant chemotherapy experienced a pCR (5.7%; 95% CI, 0.7% to 19.1%). After 5.5 years of median follow-up, four (3.7%) of the 109 patients with a PEPI = 0 score relapsed versus 49 (14.4%) of 341 of patients with PEPI > 0 (recurrence hazard ratio [PEPI = 0 v PEPI > 0], 0.27; P = .014; 95% CI, 0.092 to 0.764). Conclusion Chemotherapy efficacy was lower than expected in ER-positive tumors exhibiting AI-resistant proliferation. The optimal therapy for these patients should be further investigated. For patients with PEPI = 0 disease, the relapse risk over 5 years was only 3.6% without chemotherapy, supporting the study of adjuvant endocrine monotherapy in this group. These Ki67 and PEPI triage approaches are being definitively studied in the ALTERNATE trial (Alternate Approaches for Clinical Stage II or III Estrogen Receptor Positive Breast Cancer Neoadjuvant Treatment in Postmenopausal Women: A Phase III Study; clinical trial information: NCT01953588).

Until recently, genetic testing for hereditary breast cancer has primarily focused on pathogenic variants in the BRCA1 and BRCA2 ( BRCA) genes. However, advances in DNA sequencing technologies have made simultaneous testing for multiple genes possible. We examined correlates of interest in multigene panel testing and risk communication preferences in an ethnically diverse sample of women who tested negative for BRCA mutations previously but remain at high risk based on their family history (referred to as ' BRCA-uninformative') and their at-risk female family members. Two-hundred and thirteen women with a previous breast cancer diagnosis and a BRCA-uninformative test result and their first-degree relatives completed a survey on interest in multigene panel testing, communication preferences, and sociodemographic, psychological, and clinical factors. Stepwise logistic regression was used to identify factors associated with testing interest. Chi-square analyses were used to test differences in risk communication preferences. Interest in multigene panel testing was high (84%) and did not considerably differ by cancer status or ethnicity. In multivariable analysis, factors significantly associated with interest in genetic testing were having had a mammogram in the past 2 years (odds ratio (OR) = 4.04, 95% confidence interval (CI) 1.80-9.02) and high cancer worry (OR = 3.77, 95% CI 1.34-10.60). Overall, the most commonly preferred genetic communication modes were genetic counselors, oncologists, and print materials. However, non-Hispanic women were more likely than Hispanic women to prefer web-based risk communication ( p < 0.001). Hispanic and non-Hispanic women from BRCA-uninformative families have a high level of interest in gene panel testing. Cancer-related emotions and communication preferences should be considered in developing targeted genetic risk communication strategies. [ABSTRACT FROM AUTHOR]