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Abstract Palbociclib 3-weeks-on/1-week-off, combined with hormonal therapy, is approved for hormone receptor positive (HR+)/HER2-negative (HER2−) advanced/metastatic breast cancer (MBC). Neutropenia is the most frequent adverse event (AE). We aim to determine whether an alternative 5-days-on/2-days-off weekly schedule reduces grade 3 and above neutropenia (G3 + ANC) incidence. In this single-arm phase II trial, patients with HR+/HER2− MBC received palbociclib 125 mg, 5-days-on/2-days-off, plus letrozole or fulvestrant per physician, on a 28-day cycle (C), as their first- or second-line treatment. The primary endpoint was G3 + ANC in the first 29 days (C1). Secondary endpoints included AEs, efficacy, and serum thymidine kinase 1 (sTK1) activity. At data-cutoff, fifty-four patients received a median of 13 cycles (range 2.6–43.5). The rate of G3 + ANC was 21.3% (95% CI: 11.2–36.1%) without G4 in C1, and 40.7% (95% CI: 27.9–54.9%), including 38.9% G3 and 1.8% G4, in all cycles. The clinical benefit rate was 80.4% (95% CI: 66.5–89.7%). The median progression-free survival (mPFS) (95% CI) was 19.75 (12.11–34.89), 33.5 (17.25–not reached [NR]), and 11.96 (10.43–NR) months, in the overall, endocrine sensitive or resistant population, respectively. High sTK1 at baseline, C1 day 15 (C1D15), and C2D1 were independently prognostic for shorter PFS (p = 9.91 × 10−4, 0.001, 0.007, respectively). sTK1 decreased on C1D15 (p = 4.03 × 10−7), indicating target inhibition. Rise in sTK1 predicted progression, with the median lead time of 59.5 (inter-quartile range: −206.25–0) days. Palbociclib, 5-days-on/2-days-off weekly, met its primary endpoint with reduced G3 + ANC, without compromising efficacy. sTK1 is prognostic and shows promise in monitoring the palbociclib response. ClinicalTrials.gov#: NCT3007979.

Abstract Background Lobular carcinoma in situ (LCIS) of the breast is a risk factor of developing invasive breast cancer. We evaluated the racial differences in the risks of subsequent invasive breast cancer following LCIS. Methods We utilized data from the Surveillance, Epidemiology, and End Results registries to identify 18,835 women diagnosed with LCIS from 1990 to 2015. Cox proportional hazards regression was used to estimate race/ethnicity-associated hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of subsequent invasive breast cancer. Results During a median follow-up of 90 months, 1567 patients developed invasive breast cancer. The 10-year incidence was 7.9% for Asians, 8.2% for Hispanics, 9.3% for whites, and 11.2% for blacks (P = 0.046). Compared to white women, black women had significantly elevated risks of subsequent invasive breast cancer (HR 1.33; 95% CI 1.11, 1.59), and invasive cancer in the ipsilateral breast (HR 1.37; 95% CI 1.08, 1.72) and in the contralateral breast (HR 1.33; 95% CI 1.00, 1.76). Black women had significantly higher risks of invasive subtypes negative for both estrogen receptor and progesterone receptor (HR 1.86; 95% CI 1.14, 3.03) and invasive subtypes positive for one or both of receptors (HR 1.30; 95% CI 1.07, 1.59). The risk of subsequent invasive breast cancer was comparable in Asian women and Hispanic women compared with white women. Conclusions Black women had a significantly higher risk of developing invasive breast cancer, including both hormone receptor-positive and hormone receptor-negative subtypes, after LCIS compared with white counterparts. It provides an opportunity to address health disparities.