HER2-targeted therapy dramatically improves outcomes in early breast cancer. Here we report the results of two HER2-targeted combinations in the neoadjuvant I-SPY2 phase 2 adaptive platform trial for early breast cancer at high risk of recurrence: ado-trastuzumab emtansine plus pertuzumab (T-DM1/P) and paclitaxel, trastuzumab and pertuzumab (THP). Eligible women have >2.5 cm clinical stage II/III HER2+ breast cancer, adaptively randomized to T-DM1/P, THP, or a common control arm of paclitaxel/trastuzumab (TH), followed by doxorubicin/cyclophosphamide, then surgery. Both T-DM1/P and THP arms ‘graduate’ in all subtypes: predicted pCR rates are 63%, 72% and 33% for T-DM1/P (n = 52), THP (n = 45) and TH (n = 31) respectively. Toxicity burden is similar between arms. Degree of HER2 pathway signaling and phosphorylation in pretreatment biopsy specimens are associated with response to both T-DM1/P and THP and can further identify highly responsive HER2+ tumors to HER2-directed therapy. This may help identify patients who can safely de-escalate cytotoxic chemotherapy without compromising excellent outcome.

Dynamic contrast-enhanced (DCE) MRI provides both morphological and functional information regarding breast tumor response to neoadjuvant chemotherapy (NAC). The purpose of this retrospective study is to test if prediction models combining multiple MRI features outperform models with single features. Four features were quantitatively calculated in each MRI exam: functional tumor volume, longest diameter, sphericity, and contralateral background parenchymal enhancement. Logistic regression analysis was used to study the relationship between MRI variables and pathologic complete response (pCR). Predictive performance was estimated using the area under the receiver operating characteristic curve (AUC). The full cohort was stratified by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status (positive or negative). A total of 384 patients (median age: 49 y/o) were included. Results showed analysis with combined features achieved higher AUCs than analysis with any feature alone. AUCs estimated for the combined versus highest AUCs among single features were 0.81 (95% confidence interval [CI]: 0.76, 0.86) versus 0.79 (95% CI: 0.73, 0.85) in the full cohort, 0.83 (95% CI: 0.77, 0.92) versus 0.73 (95% CI: 0.61, 0.84) in HR-positive/HER2-negative, 0.88 (95% CI: 0.79, 0.97) versus 0.78 (95% CI: 0.63, 0.89) in HR-positive/HER2-positive, 0.83 (95% CI not available) versus 0.75 (95% CI: 0.46, 0.81) in HR-negative/HER2-positive, and 0.82 (95% CI: 0.74, 0.91) versus 0.75 (95% CI: 0.64, 0.83) in triple negatives. Multi-feature MRI analysis improved pCR prediction over analysis of any individual feature that we examined. Additionally, the improvements in prediction were more notable when analysis was conducted according to cancer subtype.

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ImportanceCancer screening deficits during the first year of the COVID-19 pandemic were found to persist into 2021. Cancer-related deaths over the next decade are projected to increase if these deficits are not addressed.ObjectiveTo assess whether participation in a nationwide quality improvement (QI) collaborative, Return-to-Screening, was associated with restoration of cancer screening.Design, Setting, and ParticipantsAccredited cancer programs electively enrolled in this QI study. Project-specific targets were established on the basis of differences in mean monthly screening test volumes (MTVs) between representative prepandemic (September 2019 and January 2020) and pandemic (September 2020 and January 2021) periods to restore prepandemic volumes and achieve a minimum of 10% increase in MTV. Local QI teams implemented evidence-based screening interventions from June to November 2021 (intervention period), iteratively adjusting interventions according to their MTVs and target. Interrupted time series analyses was used to identify the intervention effect. Data analysis was performed from January to April 2022.ExposuresCollaborative QI support included provision of a Return-to-Screening plan-do-study-act protocol, evidence-based screening interventions, QI education, programmatic coordination, and calculation of screening deficits and targets.Main Outcomes and MeasuresThe primary outcome was the proportion of QI projects reaching target MTV and counterfactual differences in the aggregate number of screening tests across time periods.ResultsOf 859 cancer screening QI projects (452 for breast cancer, 134 for colorectal cancer, 244 for lung cancer, and 29 for cervical cancer) conducted by 786 accredited cancer programs, 676 projects (79%) reached their target MTV. There were no hospital characteristics associated with increased likelihood of reaching target MTV except for disease site (lung vs breast, odds ratio, 2.8; 95% CI, 1.7 to 4.7). During the preintervention period (April to May 2021), there was a decrease in the mean MTV (slope, −13.1 tests per month; 95% CI, −23.1 to −3.2 tests per month). Interventions were associated with a significant immediate (slope, 101.0 tests per month; 95% CI, 49.1 to 153.0 tests per month) and sustained (slope, 36.3 tests per month; 95% CI, 5.3 to 67.3 tests per month) increase in MTVs relative to the preintervention trends. Additional screening tests were performed during the intervention period compared with the prepandemic period (170 748 tests), the pandemic period (210 450 tests), and the preintervention period (722 427 tests).Conclusions and RelevanceIn this QI study, participation in a national Return-to-Screening collaborative with a multifaceted QI intervention was associated with improvements in cancer screening. Future collaborative QI endeavors leveraging accreditation infrastructure may help address other gaps in cancer care.

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