2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T6f5,Patients with stage II/III human epidermal growth factor receptor 2 (HER2)-positive or triple-negative breast cancer (TNBC) frequently receive neoadjuvant therapy (NAT). Although pathologic complete response (pCR) correlates with improved outcomes, many non-pCR patients have long-term survival. Circulating tumor-DNA (ctDNA) minimal residual disease (MRD) assessment may provide additional or superior risk stratification. Pathologic Response Evaluation and Detection in Circulating Tumor-DNA is a prospective, multicenter study evaluating ctDNA as a biomarker of treatment response using a tumor-informed, ultrasensitive (<100 parts per million) assay. The primary objective was to determine whether the negative predictive value (NPV) of post-NAT ctDNA for pCR was ≥90%. A prespecified secondary objective for the TNBC cohort was to assess associations between ctDNA and 5-year invasive disease-free survival (IDFS). ctDNA was evaluated at baseline, after NAT before surgery, and after surgery. Of 227 enrolled patients, 220 were evaluable for pCR (48% HER2-positive; 52% TNBC) and 91 patients (41%) had pCR. The primary objective was not met. Although all patients with pCR were ctDNA-negative after NAT, 40% of non-pCR patients were also ctDNA-negative (NPV, 60% [95% CI, 0.50 to 0.69]). However, the prespecified secondary objective was met. Detectable ctDNA after NAT was prognostic for recurrence (hazard ratio [HR], 8.9 [95% CI, 2.4 to 33]; In HER2-positive breast cancer and TNBC, ctDNA after NAT does not discriminate pCR from non-pCR. However, ctDNA provides markedly superior prognostic stratification, identifying patients with exceptional outcomes and those at extreme risk. These findings support ctDNA-guided therapeutic de-escalation and escalation strategies.31:Tb03, PURPOSE Patients with stage II/III human epidermal growth factor receptor 2 (HER2)–positive or triple-negative breast cancer (TNBC) frequently receive neoadjuvant therapy (NAT). Although pathologic complete response (pCR) correlates with improved outcomes, many non-pCR patients have long-term survival. Circulating tumor-DNA (ctDNA) minimal residual disease (MRD) assessment may provide additional or superior risk stratification. METHODS Pathologic Response Evaluation and Detection in Circulating Tumor-DNA is a prospective, multicenter study evaluating ctDNA as a biomarker of treatment response using a tumor-informed, ultrasensitive (<100 parts per million) assay. The primary objective was to determine whether the negative predictive value (NPV) of post-NAT ctDNA for pCR was ≥90%. A prespecified secondary objective for the TNBC cohort was to assess associations between ctDNA and 5-year invasive disease-free survival (IDFS). ctDNA was evaluated at baseline, after NAT before surgery, and after surgery. RESULTS Of 227 enrolled patients, 220 were evaluable for pCR (48% HER2-positive; 52% TNBC) and 91 patients (41%) had pCR. The primary objective was not met. Although all patients with pCR were ctDNA-negative after NAT, 40% of non-pCR patients were also ctDNA-negative (NPV, 60% [95% CI, 0.50 to 0.69]). However, the prespecified secondary objective was met. Detectable ctDNA after NAT was prognostic for recurrence (hazard ratio [HR], 8.9 [95% CI, 2.4 to 33]; P = .001), independent of pCR. Additionally, detectable ctDNA after surgery identified patients at extremely high recurrence risk (HR, 128 [95% CI, 15 to 1,083]; P < .001), while ctDNA-negative patients after surgery had 94% 5-year IDFS. CONCLUSION In HER2-positive breast cancer and TNBC, ctDNA after NAT does not discriminate pCR from non-pCR. However, ctDNA provides markedly superior prognostic stratification, identifying patients with exceptional outcomes and those at extreme risk. These findings support ctDNA-guided therapeutic de-escalation and escalation strategies. 32:T6c3,Based on the results from SOLTI-PATRICIA trial (NCT02448420) cohorts A/B, a direct comparison with standard-of-care treatments is needed to evaluate the efficacy and safety of palbociclib, trastuzumab and endocrine therapy (ET) in PAM50-luminal A/B pretreated patients. SOLTI-PATRICIA cohort C is a randomised, multicentre, prospective, open-label, phase II study. Pretreated patients with HER2-positive, HR-positive, and PAM50-Luminal A/B ABC were randomised 1:1 to receive either i) the triplet regimen or ii) trastuzumab-based treatment of physician's choice (TPC). Patients allocated in the TPC arm were eligible for re-randomization upon disease progression, if the inclusion criteria were still met. The primary endpoint was investigator-assessed progression-free survival (PFS) per RECIST 1.1. 264 participants were pre-screened between August 2019-2023, and 73 patients were randomised (including seven re-randomisations). In the TPC arm: 48.5% were treated with trastuzumab plus chemotherapy, 39.4% with T-DM1 and 12.1 % with trastuzumab plus ET. The triplet was associated with a significantly better PFS compared to TPC (stratified hazard ratio=0.52 [95% CI 0.29-0.95]; two-sided p=0.03). PFS rates after 24 months were 24.0% with the triplet and 4.3% in the TPC arm. The overall response rate was 18.9% (95% CI 8.6-35.7) and 7.1% (95% CI 1.2-25.0), respectively. In the triplet arm, grade ≥3 adverse events occurred in 61.5% of patients, with neutropenia being the most frequent (53.9%). No permanent discontinuations due to toxicity were observed. Combining palbociclib, trastuzumab, and ET was safe and improved significantly PFS, compared to TPC in previously treated HER2-positive, PAM50 luminal A/B ABC patients.33:T9dc,Abstract Purpose: Based on the results from SOLTI-PATRICIA trial (NCT02448420) cohorts A/B, a direct comparison with standard-of-care treatments is needed to evaluate the efficacy and safety of palbociclib, trastuzumab, and endocrine therapy (ET) in PAM50 luminal A/B pretreated patients. Patients and Methods: SOLTI-PATRICIA cohort C is a randomized, multicenter, prospective, open-label, phase II study. Pretreated patients with HER2-positive, hormone receptor–positive, and PAM50 luminal A/B advanced breast cancer were randomized 1:1 to receive either i) the triplet regimen or ii) trastuzumab-based treatment of physician’s choice (TPC). Patients allocated in the TPC arm were eligible for re-randomization upon disease progression, if the inclusion criteria were still met. The primary endpoint was investigator-assessed progression-free survival (PFS) per RECIST version 1.1. Results: A total of 264 participants were prescreened from August 2019 to 2023, and 73 patients were randomly assigned (including seven re-randomizations). In the TPC arm, 48.5% were treated with trastuzumab plus chemotherapy, 39.4% with trastuzumab emtansine, and 12.1% with trastuzumab plus ET. The triplet was associated with a significantly better PFS compared with TPC [stratified hazard ratio = 0.52; 95% confidence interval (CI), 0.29–0.95; two-sided P = 0.03]. PFS rates after 24 months were 24.0% with the triplet and 4.3% in the TPC arm. The overall response rate was 18.9% (95% CI, 8.6–35.7) and 7.1% (95% CI, 1.2–25.0), respectively. In the triplet arm, grade ≥3 adverse events occurred in 61.5% of patients, with neutropenia being the most frequent (53.9%). No permanent discontinuations due to toxicity were observed. Conclusions: Combining palbociclib, trastuzumab, and ET was safe and significantly improved PFS, compared with TPC, in previously treated patients with HER2-positive, PAM50 luminal A/B advanced breast cancer. 25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"HER2-Positive Breast Cancer: condition Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on HER2-Positive Breast Cancer (condition). Clinician-written summaries and actionable practice insights. 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OS data were immature (medians not reached; HR 0.62, 95% CI 0.38–1.03). Grade ≥3 TEAEs occurred in 69.8% vs. 63.7%; ocular adverse events were notably more frequent with trastuzumab botidotin but generally resolved with a protocol-defined management algorithm.","limitations":"- OS data were immature at data cutoff, limiting conclusions on survival benefit.\n- Trial conducted exclusively in China, which may limit generalizability to other populations.\n- Open-label design introduces potential for performance and assessment bias.","practice_takeaway":"In HER2-positive metastatic breast cancer after trastuzumab and taxane exposure, trastuzumab botidotin nearly tripled median PFS compared to T-DM1 — clinicians should be aware of its higher rate of ocular toxicity and follow a structured monitoring and management algorithm."}},{"doi":"10.1200/jco-26-01423","pmid":"42715513","title":"Risk-Adapted Optimization of Neoadjuvant Therapy in Human Epidermal Growth Factor Receptor 2–Positive Early-Stage Breast Cancer","journal_title":"Journal of Clinical Oncology","journal_issn":"0732-183X","published_at":"2026-09-09T00:00:00.000Z","url":"https://doi.org/10.1200/jco-26-01423","source_score":45,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-14T06:23:26.751Z","updated_at":"2026-09-14T06:23:26.751Z","tags":[{"paper_doi":"10.1200/jco-26-01423","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1200/jco-26-01423","tag_type":"brand","value":"Enhertu","value_numeric":null},{"paper_doi":"10.1200/jco-26-01423","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1200/jco-26-01423","tag_type":"condition","value":"HER2-Positive Breast Cancer","value_numeric":null},{"paper_doi":"10.1200/jco-26-01423","tag_type":"generic","value":"carboplatin","value_numeric":null},{"paper_doi":"10.1200/jco-26-01423","tag_type":"generic","value":"docetaxel","value_numeric":null},{"paper_doi":"10.1200/jco-26-01423","tag_type":"generic","value":"fam-trastuzumab deruxtecan-nxki","value_numeric":null},{"paper_doi":"10.1200/jco-26-01423","tag_type":"generic","value":"paclitaxel","value_numeric":null},{"paper_doi":"10.1200/jco-26-01423","tag_type":"generic","value":"pertuzumab","value_numeric":null},{"paper_doi":"10.1200/jco-26-01423","tag_type":"generic","value":"trastuzumab","value_numeric":null},{"paper_doi":"10.1200/jco-26-01423","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1200/jco-26-01423","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1200/jco-26-01423","tag_type":"modality","value":"Antibody-Drug Conjugate","value_numeric":null},{"paper_doi":"10.1200/jco-26-01423","tag_type":"modality","value":"Chemotherapy","value_numeric":null},{"paper_doi":"10.1200/jco-26-01423","tag_type":"modality","value":"HER2-Targeted Therapy","value_numeric":null},{"paper_doi":"10.1200/jco-26-01423","tag_type":"sex","value":"female","value_numeric":null},{"paper_doi":"10.1200/jco-26-01423","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1200/jco-26-01423","tag_type":"warning","value":"Biomarker-guided de-escalation strategies (ctDNA monitoring, functional imaging) are discussed as investigational priorities, not yet standard of care.","value_numeric":null},{"paper_doi":"10.1200/jco-26-01423","tag_type":"warning","value":"No sample size tag applied as this is a review article with no single enrolled patient cohort.","value_numeric":null},{"paper_doi":"10.1200/jco-26-01423","tag_type":"warning","value":"This is a narrative review; conclusions about de-escalation are based on cited randomized trials (e.g., DESTINY-Breast11, DESTINY-Breast05) rather than original data presented here — readers should consult the primary trial publications for full efficacy and safety details.","value_numeric":null}],"summaries":{"what_studied":"This review evaluates risk-adapted neoadjuvant and postneoadjuvant treatment strategies for stage II–III HER2-positive early-stage breast cancer, including de-escalation approaches (omitting carboplatin, chemotherapy-free regimens) and escalation options (fam-trastuzumab deruxtecan-nxki), informed by biomarkers such as circulating tumor DNA and functional imaging.","key_result":"Randomized trial data support omitting carboplatin from neoadjuvant therapy for most stage II HER2-positive patients with comparable pathological complete response (pCR) rates and reduced toxicity; DESTINY-Breast11 and DESTINY-Breast05 established neoadjuvant and postneoadjuvant T-DXd, respectively, as FDA-approved options for high-risk disease.","limitations":"This is a narrative review, not a primary trial; no new efficacy or safety data are generated. Biomarker-guided strategies (ctDNA, functional imaging) are identified as priorities for future investigation rather than established practice.","practice_takeaway":"For most patients with stage II HER2-positive breast cancer, carboplatin can be dropped from neoadjuvant therapy (moving from TCHP to THP-based regimens) without sacrificing pCR rates. For high-risk patients, T-DXd now has FDA approval in both the neoadjuvant and postneoadjuvant settings and should be considered in treatment planning."}},{"doi":"10.1111/1759-7714.70379","pmid":"42601812","title":"Exceptional Response of\n HER2\n ‐Positive Breast Cancer to Osimertinib: A Case Report","journal_title":"Thoracic Cancer","journal_issn":"1759-7706","published_at":"2026-08-14T00:00:00.000Z","url":"https://doi.org/10.1111/1759-7714.70379","source_score":1,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-26T06:20:02.645Z","updated_at":"2026-08-26T06:20:02.645Z","tags":[{"paper_doi":"10.1111/1759-7714.70379","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1111/1759-7714.70379","tag_type":"brand","value":"Tagrisso","value_numeric":null},{"paper_doi":"10.1111/1759-7714.70379","tag_type":"category","value":"Respiratory System","value_numeric":null},{"paper_doi":"10.1111/1759-7714.70379","tag_type":"condition","value":"EGFR-Mutant Non-Small Cell Lung Cancer","value_numeric":null},{"paper_doi":"10.1111/1759-7714.70379","tag_type":"condition","value":"HER2-Positive Breast Cancer","value_numeric":null},{"paper_doi":"10.1111/1759-7714.70379","tag_type":"generic","value":"osimertinib","value_numeric":null},{"paper_doi":"10.1111/1759-7714.70379","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1111/1759-7714.70379","tag_type":"level_of_evidence","value":"7","value_numeric":null},{"paper_doi":"10.1111/1759-7714.70379","tag_type":"modality","value":"EGFR Tyrosine Kinase Inhibitor","value_numeric":null},{"paper_doi":"10.1111/1759-7714.70379","tag_type":"sample_size","value":"n=1","value_numeric":1},{"paper_doi":"10.1111/1759-7714.70379","tag_type":"sex","value":"female","value_numeric":null},{"paper_doi":"10.1111/1759-7714.70379","tag_type":"study_design","value":"Case Report","value_numeric":null},{"paper_doi":"10.1111/1759-7714.70379","tag_type":"warning","value":"Baseline HER2 FISH was not performed, so it is unknown whether HER2 amplification was present before osimertinib; post-treatment biopsy was obtained after a six-month drug-free interval.","value_numeric":null},{"paper_doi":"10.1111/1759-7714.70379","tag_type":"warning","value":"Only one patient reported; findings cannot be generalized or used to guide treatment decisions.","value_numeric":null},{"paper_doi":"10.1111/1759-7714.70379","tag_type":"warning","value":"The exact mechanism (osimertinib vs. its metabolite AZ5104 vs. spontaneous tumor biology) is unproven; no functional validation was performed.","value_numeric":null},{"paper_doi":"10.1111/1759-7714.70379","tag_type":"warning","value":"The paper references two similar 2026 case reports of osimertinib-associated DCIS regression, suggesting an emerging pattern, but evidence remains anecdotal.","value_numeric":null}],"summaries":{"what_studied":"An 83-year-old woman with synchronous EGFR L858R-mutant lung adenocarcinoma (stage IVB) and HER2 IHC 3+ invasive breast cancer (stage IIA) was treated with osimertinib monotherapy; breast cancer response was observed over 27 months without dedicated HER2-directed therapy.","key_result":"The breast lesion shrank from 31×20 mm to 13×10 mm at 3 months and showed sustained metabolic response at 21 months (SUVmax 0.99 vs. 7.55 at baseline); postmortem biopsy confirmed Grade 3 therapeutic effect with HER2 amplification (HER2/CEP17 ratio 3.16), Ki-67 drop from 20% to 10%, and negative pAKT/pERK.","limitations":"- No baseline HER2 FISH, so pre-treatment amplification status cannot be compared.\n- Serial tissue or liquid biopsy was unavailable; clonal evolution and resistance mechanisms could not be tracked.\n- Single case without functional validation; findings are hypothesis-generating only.","practice_takeaway":"This case does **not** support using osimertinib as a substitute for established HER2-directed therapy in breast cancer. Clinicians managing synchronous EGFR-mutant lung and HER2-positive breast cancers should be aware of this possible off-target effect, but breast cancer treatment decisions should follow current evidence-based guidelines."}},{"doi":"10.1001/jamaoncol.2026.2023","pmid":"42348190","title":"Neoadjuvant Paclitaxel, Trastuzumab, and Pertuzumab for Stage II to III,\n ERBB2\n -Positive Breast Cancer","journal_title":"JAMA Oncology","journal_issn":"2374-2437","published_at":"2026-06-25T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13306490/","source_score":19,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-03T13:38:39.935Z","updated_at":"2026-07-03T13:38:39.935Z","tags":[{"paper_doi":"10.1001/jamaoncol.2026.2023","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1001/jamaoncol.2026.2023","tag_type":"brand","value":"Herceptin","value_numeric":null},{"paper_doi":"10.1001/jamaoncol.2026.2023","tag_type":"brand","value":"Perjeta","value_numeric":null},{"paper_doi":"10.1001/jamaoncol.2026.2023","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1001/jamaoncol.2026.2023","tag_type":"condition","value":"HER2-Positive Breast Cancer","value_numeric":null},{"paper_doi":"10.1001/jamaoncol.2026.2023","tag_type":"generic","value":"paclitaxel","value_numeric":null},{"paper_doi":"10.1001/jamaoncol.2026.2023","tag_type":"generic","value":"pertuzumab","value_numeric":null},{"paper_doi":"10.1001/jamaoncol.2026.2023","tag_type":"generic","value":"trastuzumab","value_numeric":null},{"paper_doi":"10.1001/jamaoncol.2026.2023","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1001/jamaoncol.2026.2023","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1001/jamaoncol.2026.2023","tag_type":"modality","value":"HER2-Targeted Therapy","value_numeric":null},{"paper_doi":"10.1001/jamaoncol.2026.2023","tag_type":"modality","value":"Taxane","value_numeric":null},{"paper_doi":"10.1001/jamaoncol.2026.2023","tag_type":"sample_size","value":"n=98","value_numeric":98},{"paper_doi":"10.1001/jamaoncol.2026.2023","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamaoncol.2026.2023","tag_type":"study_design","value":"Non-Randomized Clinical Trial (Phase 2, Single-Arm)","value_numeric":null},{"paper_doi":"10.1001/jamaoncol.2026.2023","tag_type":"warning","value":"The ctDNA substudy (n=57) is a subset of the full trial cohort (n=98); findings may not fully represent the overall population. The study does not report what proportion of patients received adjuvant T-DM1 vs. other therapies, which could confound outcome interpretation. The single male patient means sex-based subgroup conclusions are not possible.","value_numeric":null}],"summaries":{"what_studied":"The DAPHNe phase 2 single-arm trial evaluated 5-year outcomes and ultrasensitive ctDNA dynamics in 98 patients with stage II–III ERBB2-positive breast cancer receiving 12 weeks of neoadjuvant paclitaxel, trastuzumab, and pertuzumab (THP), followed by response-guided adjuvant therapy (median follow-up 5.2 years).","key_result":"At 5 years: event-free survival 99%, recurrence-free interval 98%, distant recurrence-free interval 100%, and overall survival 99%. Among 57 patients with ctDNA data, baseline ctDNA was detected in 89.5% (51/57); after neoadjuvant THP, 96.1% (49/51) cleared ctDNA preoperatively. Only one local recurrence occurred across the cohort.","limitations":"Single-arm, non-randomized design with no comparator group limits causal inference. ctDNA substudy included only 57 of 98 patients (tissue/plasma availability required), introducing potential selection bias. Predominantly stage II (92.9%) and mostly female (99%) cohort limits generalizability to stage III or male patients.","practice_takeaway":"Abbreviated 12-week neoadjuvant THP shows excellent 5-year outcomes for early-stage HER2-positive breast cancer, supporting its use as a chemotherapy-sparing option. Near-universal ctDNA clearance after therapy suggests ctDNA-guided de-escalation strategies warrant prospective randomized study."}},{"doi":"10.1016/j.breast.2026.104849","pmid":"42391855","title":"HER2DX genomic assay in HER2-positive early breast cancer treated with trastuzumab and pertuzumab: A correlative analysis from a real-world cohort","journal_title":"The Breast","journal_issn":"0960-9776","published_at":"2026-06-23T00:00:00.000Z","url":"https://doi.org/10.1016/j.breast.2026.104849","source_score":8,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-04T13:26:24.219Z","updated_at":"2026-07-04T13:26:24.219Z","tags":[{"paper_doi":"10.1016/j.breast.2026.104849","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104849","tag_type":"brand","value":"Herceptin","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104849","tag_type":"brand","value":"Perjeta","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104849","tag_type":"category","value":"Obstetrics & Gynecology","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104849","tag_type":"condition","value":"Early Breast Cancer","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104849","tag_type":"condition","value":"HER2-Positive Breast Cancer","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104849","tag_type":"generic","value":"pertuzumab","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104849","tag_type":"generic","value":"trastuzumab","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104849","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104849","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104849","tag_type":"modality","value":"Genomic Assay","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104849","tag_type":"modality","value":"HER2-Targeted Therapy","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104849","tag_type":"sample_size","value":"n=156","value_numeric":156},{"paper_doi":"10.1016/j.breast.2026.104849","tag_type":"sex","value":"female","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104849","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104849","tag_type":"warning","value":"HER2DX assay was performed in only 111 of 156 patients (71.2%), which may introduce selection bias in the genomic score analyses.","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104849","tag_type":"warning","value":"Median IDFS was not reached; survival estimates should be interpreted with caution given the relatively short follow-up implied.","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104849","tag_type":"warning","value":"The HER2DX pCR continuous score was not independently significant in multivariable analysis, suggesting the pCR score's independent predictive value in this real-world cohort is uncertain.","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104849","tag_type":"warning","value":"The study is from a single center in Spain, which may limit generalizability to other healthcare settings or populations.","value_numeric":null}],"summaries":{"what_studied":"This retrospective, single-center study evaluated the HER2DX genomic assay in 156 patients with stage I–III HER2-positive early breast cancer treated with dual HER2 blockade (trastuzumab + pertuzumab)-based neoadjuvant therapy between February 2015 and May 2022, examining associations with pathological complete response (pCR) and invasive disease-free survival (IDFS).","key_result":"Overall pCR rate was 51.3% (n=156). Medium-high HER2DX pCR category had significantly higher pCR than the low category (OR 4.83, 95% CI 1.72–14.65; p=0.004). The continuous HER2DX risk score was independently associated with IDFS (HR 2.84, 95% CI 1.24–6.48; p=0.010). Hormone receptor-positive disease was strongly associated with lower pCR (OR 0.25, 95% CI 0.11–0.50; p<0.001) but better IDFS (HR 3.67 for HR-negative vs. HR-positive; p=0.004).","limitations":"- Single-center, retrospective design with modest sample size (n=111 with HER2DX data), limiting generalizability.\n- HER2DX pCR score lost significance in multivariable analysis, suggesting possible confounding or limited independent predictive value in this cohort.\n- Median IDFS was not reached, making long-term survival conclusions preliminary.","practice_takeaway":"The HER2DX risk score may help identify HER2-positive early breast cancer patients at higher risk of recurrence after dual HER2 blockade-based neoadjuvant therapy, supporting its potential role in treatment stratification. Clinicians should note that hormone receptor status remains a key modifier of both pCR and survival outcomes in this setting."}},{"doi":"10.1158/2159-8290.cd-25-1459","pmid":"41925564","title":"HER2 Heterogeneous Breast Cancer Models Reveal Novel Therapeutic Targets and Subclonal Dynamics during Evolution to Resistance to HER2-Targeted Therapies","journal_title":"Cancer Discovery","journal_issn":"2159-8274","published_at":"2026-06-17T00:00:00.000Z","url":"https://doi.org/10.1158/2159-8290.cd-25-1459","source_score":32,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-20T13:25:04.149Z","updated_at":"2026-06-20T13:25:04.149Z","tags":[{"paper_doi":"10.1158/2159-8290.cd-25-1459","tag_type":"brand","value":"Enhertu","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-1459","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-1459","tag_type":"condition","value":"HER2-Positive Breast Cancer","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-1459","tag_type":"condition","value":"Intratumor Heterogeneity","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-1459","tag_type":"generic","value":"trastuzumab deruxtecan","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-1459","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-1459","tag_type":"level_of_evidence","value":"6","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-1459","tag_type":"modality","value":"Antibody-Drug Conjugate","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-1459","tag_type":"modality","value":"CRISPR Screen","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-1459","tag_type":"modality","value":"HER2 Kinase Inhibitor","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-1459","tag_type":"modality","value":"USP9X Inhibitor","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-1459","tag_type":"study_design","value":"Preclinical Laboratory Study","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-1459","tag_type":"warning","value":"No sample size (N) is reportable as this is a cell/model-based study without a defined patient cohort.","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-1459","tag_type":"warning","value":"Study design is categorized as 'Preclinical Laboratory Study'; no standard RCT or observational design applies.","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-1459","tag_type":"warning","value":"T-DXd is listed under its brand name 'Enhertu' (trastuzumab deruxtecan); the paper uses the abbreviation 'T-DXd' throughout.","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-1459","tag_type":"warning","value":"The impact_flag 'practice_changing' reflects the novelty of the USP9X finding and its therapeutic implications, but this is entirely preclinical — no patient data are presented; clinical translation is speculative at this stage.","value_numeric":null}],"summaries":{"limitations":"Findings are from preclinical (in vitro/cell line) models only — clinical validation in patients is lacking; models may not fully capture the spatial and clonal complexity of HER2 heterogeneity in human tumors.","practice_takeaway":"HER2 intratumor heterogeneity is a key driver of T-DXd resistance; USP9X inhibition is a candidate strategy to re-sensitize HER2lo clones to T-DXd and warrants clinical investigation. Clinicians should consider HER2 heterogeneity when sequencing or combining HER2-targeted therapies.","what_studied":"This preclinical study used human HER2-heterogeneous breast cancer models (paired ERBB2-amplified HER2hi and non-amplified HER2lo cell populations from the same tumor) with cellular barcoding and CRISPR screens to map subclonal dynamics and identify resistance mechanisms to HER2-targeted ADCs (T-DXd) and kinase inhibitors.","key_result":"HER2lo subpopulations drove resistance to T-DXd but remained sensitive to HER2 kinase inhibitors; CRISPR screens identified ABCC1 and USP9X as T-DXd sensitizers in HER2lo cells, and USP9X inhibition enhanced lysosomal HER2 targeting, boosting ADC payload release and reducing tumor recurrence after T-DXd treatment."}},{"doi":"10.1080/14737140.2026.2682866","pmid":"42216244","title":"Polypharmacy, polypharmacology, and polypharmacotherapy: clarifying definitions and complementary roles in cancer treatment – a narrative review","journal_title":"Expert Review of Anticancer Therapy","journal_issn":"1473-7140","published_at":"2026-06-02T00:00:00.000Z","url":"https://doi.org/10.1080/14737140.2026.2682866","source_score":2,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-08T13:46:38.436Z","updated_at":"2026-06-08T13:46:38.436Z","tags":[{"paper_doi":"10.1080/14737140.2026.2682866","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1080/14737140.2026.2682866","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1080/14737140.2026.2682866","tag_type":"condition","value":"Cancer","value_numeric":null},{"paper_doi":"10.1080/14737140.2026.2682866","tag_type":"condition","value":"Chronic Myeloid Leukemia","value_numeric":null},{"paper_doi":"10.1080/14737140.2026.2682866","tag_type":"condition","value":"HER2-Positive Breast Cancer","value_numeric":null},{"paper_doi":"10.1080/14737140.2026.2682866","tag_type":"condition","value":"Melanoma","value_numeric":null},{"paper_doi":"10.1080/14737140.2026.2682866","tag_type":"condition","value":"Renal Cell Carcinoma","value_numeric":null},{"paper_doi":"10.1080/14737140.2026.2682866","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1080/14737140.2026.2682866","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1080/14737140.2026.2682866","tag_type":"modality","value":"Drug Repurposing","value_numeric":null},{"paper_doi":"10.1080/14737140.2026.2682866","tag_type":"modality","value":"Multitarget-Directed Ligand","value_numeric":null},{"paper_doi":"10.1080/14737140.2026.2682866","tag_type":"modality","value":"Targeted Therapy","value_numeric":null},{"paper_doi":"10.1080/14737140.2026.2682866","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1080/14737140.2026.2682866","tag_type":"warning","value":"Full text was not available; summary is based on the abstract and article highlights only. Some details (e.g., specific drugs discussed, depth of evidence review) may not be fully captured.","value_numeric":null},{"paper_doi":"10.1080/14737140.2026.2682866","tag_type":"warning","value":"No sample size tag applied — this is a review with no primary patient cohort.","value_numeric":null},{"paper_doi":"10.1080/14737140.2026.2682866","tag_type":"warning","value":"The 5.2% success rate and 2.8-month survival figures are cited from referenced external analyses, not generated by this review's own analysis.","value_numeric":null}],"summaries":{"what_studied":"This narrative review clarifies and distinguishes three concepts — polypharmacy, polypharmacology, and polypharmacotherapy — and examines their complementary roles in cancer treatment, with attention to drug repurposing and multitarget strategies as alternatives or adjuncts to precision oncology guided by the Somatic Mutation Theory (SMT).","key_result":"SMT-based precision oncology shows limited overall impact: a ~5.2% drug development success rate and a median overall survival benefit of only 2.8 months across 124 FDA-approved drugs (374 indications) from 2003–2021. The review argues polypharmacotherapy — using multiple repurposed non-oncology drugs targeting diverse pathways — offers a pragmatic, equitable complement to this approach.","limitations":"As a narrative (not systematic) review, it is subject to selection bias in the literature covered. No original clinical data are presented, and the efficacy of polypharmacotherapy remains to be validated in formal clinical trials, which the authors themselves identify as urgently needed.","practice_takeaway":"Clinicians should be aware that polypharmacy (multi-drug comorbidity management), polypharmacology (single multitarget drugs), and polypharmacotherapy (multi-drug cancer pathway targeting, often via repurposed agents) are distinct concepts with different risk-benefit profiles. Repurposed non-oncology drugs used in combination represent a low-cost, potentially more equitable strategy worth considering in trial design, especially for patients with limited access to targeted therapies."}},{"doi":"10.1016/j.annonc.2026.05.700","pmid":"42203036","title":"Predicting neoadjuvant breast cancer therapy response using BRIDGE from tumor transcriptomics and histopathology","journal_title":"Annals of Oncology","journal_issn":"0923-7534","published_at":"2026-05-26T00:00:00.000Z","url":"https://doi.org/10.1016/j.annonc.2026.05.700","source_score":12,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-05T13:26:37.724Z","updated_at":"2026-06-05T13:26:37.724Z","tags":[{"paper_doi":"10.1016/j.annonc.2026.05.700","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.annonc.2026.05.700","tag_type":"brand","value":"MammaPrint","value_numeric":null},{"paper_doi":"10.1016/j.annonc.2026.05.700","tag_type":"brand","value":"Oncotype DX","value_numeric":null},{"paper_doi":"10.1016/j.annonc.2026.05.700","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1016/j.annonc.2026.05.700","tag_type":"condition","value":"Breast Cancer","value_numeric":null},{"paper_doi":"10.1016/j.annonc.2026.05.700","tag_type":"condition","value":"ER-Positive HER2-Negative Breast Cancer","value_numeric":null},{"paper_doi":"10.1016/j.annonc.2026.05.700","tag_type":"condition","value":"HER2-Positive Breast Cancer","value_numeric":null},{"paper_doi":"10.1016/j.annonc.2026.05.700","tag_type":"condition","value":"Triple-Negative Breast Cancer","value_numeric":null},{"paper_doi":"10.1016/j.annonc.2026.05.700","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/j.annonc.2026.05.700","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1016/j.annonc.2026.05.700","tag_type":"modality","value":"Deep Learning / Computational Pathology","value_numeric":null},{"paper_doi":"10.1016/j.annonc.2026.05.700","tag_type":"modality","value":"Immune Checkpoint Blockade","value_numeric":null},{"paper_doi":"10.1016/j.annonc.2026.05.700","tag_type":"modality","value":"Neoadjuvant Chemotherapy","value_numeric":null},{"paper_doi":"10.1016/j.annonc.2026.05.700","tag_type":"modality","value":"Transcriptomic Biomarker","value_numeric":null},{"paper_doi":"10.1016/j.annonc.2026.05.700","tag_type":"sex","value":"female","value_numeric":null},{"paper_doi":"10.1016/j.annonc.2026.05.700","tag_type":"study_design","value":"Computational Modeling / Retrospective Validation Study","value_numeric":null},{"paper_doi":"10.1016/j.annonc.2026.05.700","tag_type":"warning","value":"Commercial signature comparisons used surrogate (re-implemented) versions of Oncotype DX, MammaPrint, and ROR-S, not the validated proprietary algorithms — results may not fully reflect real-world performance of those tools.","value_numeric":null},{"paper_doi":"10.1016/j.annonc.2026.05.700","tag_type":"warning","value":"Full text was not accessible; findings are based on the abstract and results section only — sample sizes per individual cohort and absolute pCR rates are unverified.","value_numeric":null},{"paper_doi":"10.1016/j.annonc.2026.05.700","tag_type":"warning","value":"Study design tag reflects a computational/ML framework trained and validated retrospectively across multiple cohorts; no single standard label perfectly captures this design.","value_numeric":null},{"paper_doi":"10.1016/j.annonc.2026.05.700","tag_type":"warning","value":"The 'practice_changing' impact flag is applied cautiously: BRIDGE shows strong retrospective performance, but the authors explicitly state prospective validation is still required.","value_numeric":null}],"summaries":{"what_studied":"BRIDGE, a computational framework using pre-treatment bulk tumor transcriptomics deconvolution to predict pathological complete response (pCR) to neoadjuvant therapy in breast cancer, was trained on 10 transcriptomics datasets and tested on 24 independent cohorts across ER+/HER2-, HER2+, and TNBC subtypes; a histopathology-based version (BRIDGE-Slide) using deep learning-inferred transcriptomics from H&E slides was evaluated in 6 additional datasets.","key_result":"BRIDGE outperformed surrogate implementations of Oncotype DX, MammaPrint, and ROR-S in ER+/HER2- tumors (AUC 0.84, OR 8.0), and surpassed other transcriptomic predictors in HER2+ (AUC 0.77, OR 8.3) and TNBC (AUC 0.73, OR 3.1); BRIDGE-Slide outperformed direct slide-to-response models across all subtypes.","limitations":"- BRIDGE-Slide and ICB generalizability findings are exploratory and require prospective validation in larger cohorts.\n- Commercial signatures (Oncotype DX, MammaPrint, ROR-S) were compared as surrogate implementations, not head-to-head using their actual proprietary algorithms.\n- Full text was not available; sample sizes per cohort and absolute pCR rates could not be verified.","practice_takeaway":"BRIDGE may improve pCR prediction before neoadjuvant breast cancer therapy across all major subtypes, with the H&E slide-based version (BRIDGE-Slide) offering a potentially fast, low-cost alternative to molecular testing. Prospective validation is needed before clinical adoption."}},{"doi":"10.1158/0008-5472.can-25-2569","pmid":"41954631","title":"An Analytic Framework Characterizes the Biological Processes That Shape Copy Number–Based Genome Instability Patterns in Breast Cancer","journal_title":"Cancer Research","journal_issn":"0008-5472","published_at":"2026-05-14T00:00:00.000Z","url":"https://doi.org/10.1158/0008-5472.can-25-2569","source_score":62,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-23T13:25:02.080Z","updated_at":"2026-05-23T13:25:02.080Z","tags":[{"paper_doi":"10.1158/0008-5472.can-25-2569","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1158/0008-5472.can-25-2569","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1158/0008-5472.can-25-2569","tag_type":"condition","value":"Breast Cancer","value_numeric":null},{"paper_doi":"10.1158/0008-5472.can-25-2569","tag_type":"condition","value":"HER2-Positive Breast Cancer","value_numeric":null},{"paper_doi":"10.1158/0008-5472.can-25-2569","tag_type":"condition","value":"Homologous Recombination Deficiency","value_numeric":null},{"paper_doi":"10.1158/0008-5472.can-25-2569","tag_type":"generic","value":"PARP inhibitor","value_numeric":null},{"paper_doi":"10.1158/0008-5472.can-25-2569","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1158/0008-5472.can-25-2569","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1158/0008-5472.can-25-2569","tag_type":"modality","value":"Copy Number Signature Analysis","value_numeric":null},{"paper_doi":"10.1158/0008-5472.can-25-2569","tag_type":"modality","value":"Genomic Profiling","value_numeric":null},{"paper_doi":"10.1158/0008-5472.can-25-2569","tag_type":"modality","value":"Tumor Microenvironment Analysis","value_numeric":null},{"paper_doi":"10.1158/0008-5472.can-25-2569","tag_type":"sample_size","value":"n=2763","value_numeric":2763},{"paper_doi":"10.1158/0008-5472.can-25-2569","tag_type":"sex","value":"female","value_numeric":null},{"paper_doi":"10.1158/0008-5472.can-25-2569","tag_type":"study_design","value":"Retrospective Genomic Analysis","value_numeric":null},{"paper_doi":"10.1158/0008-5472.can-25-2569","tag_type":"warning","value":"No specific drug interventions were tested; the PARP inhibitor generic tag reflects the biological relevance of HRD signatures to that drug class, not a direct drug study.","value_numeric":null},{"paper_doi":"10.1158/0008-5472.can-25-2569","tag_type":"warning","value":"Study design is best described as a retrospective computational/genomic analysis; it does not fit neatly into standard clinical trial design categories.","value_numeric":null},{"paper_doi":"10.1158/0008-5472.can-25-2569","tag_type":"warning","value":"The 'practice_changing' impact flag is applied cautiously — findings are derived from retrospective cohorts and have not yet been validated in prospective clinical trials. The survival benefit in CN-quiet/low-macrophage patients is associative, not causal.","value_numeric":null}],"summaries":{"what_studied":"This study developed an analytic framework to characterize copy number alteration (CNA) patterns and genome instability (GI) in 2,763 breast cancer genomes (TCGA and METABRIC), using pre-defined CN-based GI scores alongside de novo CN signature extraction across immunohistochemical subtypes.","key_result":"Eight CN signatures were identified: three linked to distinct homologous recombination deficiency (HRD) features with differential activity in BRCA1 vs. BRCA2-loss tumors; one HER2+-enriched signature overlapped heavily with chromothripsis and circular extrachromosomal DNA regions; CN-quiet diploid/tetraploid subtypes were defined, with tetraploid tumors enriched for PIK3CA, MAP3K1, and CDH1 mutations; patients with quiet genomes and low macrophage infiltration had notably better survival outcomes.","limitations":"Analysis is limited to two retrospective cohorts (TCGA and METABRIC), restricting causal inference; findings are association-based and may not generalize across other cancer types or sequencing platforms without further validation.","practice_takeaway":"CN signature profiling alongside tumor microenvironment data (especially macrophage infiltration) may help risk-stratify breast cancer patients — those with CN-quiet genomes and low macrophage infiltration appear to have markedly better survival. Distinct HRD signatures for BRCA1 vs. BRCA2 loss could eventually refine treatment selection for HRD-targeted therapies."}},{"doi":"10.1200/jco-25-02934","pmid":"41805422","title":"The Pathologic Response Evaluation and Detection in Circulating Tumor-DNA Study: Ultrasensitive Circulating Tumor-DNA Assessment of Breast Cancer Minimal Residual Disease","journal_title":"Journal of Clinical Oncology","journal_issn":"0732-183X","published_at":"2026-03-10T00:00:00.000Z","url":"https://doi.org/10.1200/jco-25-02934","source_score":54,"is_retracted":false,"is_open_access":false,"raw_metadata":{"ooir":{"day":"2026-05-08","doi":"10.1200/jco-25-02934","days":"7","issn":"0732-183X","rank":"3","field":"Clinical Medicine","score":"54","category":"Oncology","categories":["Oncology"],"_categories":["Oncology"]},"pubmed":{"doi":"10.1200/JCO-25-02934","title":"The Pathologic Response Evaluation and Detection in Circulating Tumor-DNA Study: Ultrasensitive Circulating Tumor-DNA Assessment of Breast Cancer Minimal Residual Disease.","journal":"Journal of clinical oncology : official journal of the American Society of Clinical Oncology","methods":"","results":"Of 227 enrolled patients, 220 were evaluable for pCR (48% HER2-positive; 52% TNBC) and 91 patients (41%) had pCR. The primary objective was not met. Although all patients with pCR were ctDNA-negative after NAT, 40% of non-pCR patients were also ctDNA-negative (NPV, 60% [95% CI, 0.50 to 0.69]). However, the prespecified secondary objective was met. Detectable ctDNA after NAT was prognostic for recurrence (hazard ratio [HR], 8.9 [95% CI, 2.4 to 33]; ","abstract":"$30","keywords":[],"pubmed_id":"41805422","conclusions":"In HER2-positive breast cancer and TNBC, ctDNA after NAT does not discriminate pCR from non-pCR. However, ctDNA provides markedly superior prognostic stratification, identifying patients with exceptional outcomes and those at extreme risk. These findings support ctDNA-guided therapeutic de-escalation and escalation strategies.","publication_date":"2026-03-10T00:00:00"},"crossref":{"DOI":"10.1200/jco-25-02934","URL":"https://doi.org/10.1200/jco-25-02934","ISSN":["0732-183X","1527-7755"],"link":[{"URL":"https://ascopubs.org/doi/pdfdirect/10.1200/JCO-25-02934","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":"1283-1295","type":"journal-article","issue":"14","score":1,"title":["The Pathologic Response Evaluation and Detection in Circulating Tumor-DNA Study: Ultrasensitive Circulating Tumor-DNA Assessment of Breast Cancer Minimal Residual Disease"],"author":[{"given":"Natasha B.","family":"Hunter","sequence":"first","affiliation":[{"name":"Fred Hutchinson Cancer Center, University of Washington, Seattle, WA"}]},{"given":"Heather A.","family":"Parsons","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Center, University of Washington, Seattle, WA"},{"name":"Dana Farber Cancer Institute, Boston, MA"}]},{"given":"Leslie","family":"Cope","sequence":"additional","affiliation":[{"name":"Johns Hopkins University, Baltimore, MD"}]},{"given":"Jenna V.","family":"Canzoniero","sequence":"additional","affiliation":[{"name":"Johns Hopkins University, Baltimore, MD"}]},{"given":"Fabio C.P.","family":"Navarro","sequence":"additional","affiliation":[{"name":"Personalis, Fremont, CA"}]},{"given":"Sherif","family":"El-Refai","sequence":"additional","affiliation":[{"name":"Personalis, Fremont, CA"}]},{"given":"Jesus D.","family":"Anampa","sequence":"additional","affiliation":[{"name":"Montefiore Einstein Comprehensive Cancer Center, Bronx, NY"}]},{"given":"Joseph A.","family":"Sparano","sequence":"additional","affiliation":[{"name":"Montefiore Einstein Comprehensive Cancer Center, Bronx, NY"}]},{"given":"Mothaffar","family":"Rimawi","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine, Houston, TX"}]},{"given":"Anna Maria","family":"Storniolo","sequence":"additional","affiliation":[{"name":"Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN"}]},{"given":"Candace","family":"Mainor","sequence":"additional","affiliation":[{"name":"Medstar Georgetown University-Hospital-Lombardi Comprehensive Cancer Center, Washington, DC"}]},{"given":"Rita","family":"Nanda","sequence":"additional","affiliation":[{"name":"University of Chicago, Chicago, IL"}]},{"given":"Angela","family":"DeMichele","sequence":"additional","affiliation":[{"name":"University of Pennsylvania, Philadelphia, PA"}]},{"given":"Gaorav P.","family":"Gupta","sequence":"additional","affiliation":[{"name":"University of North Carolina, Chapel Hill, NC"}]},{"given":"Erica J.","family":"Stringer-Reasor","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham, Birmingham, AL"}]},{"given":"Filipa","family":"Lynce","sequence":"additional","affiliation":[{"name":"Dana Farber Cancer Institute, Boston, MA"},{"name":"Medstar Georgetown University-Hospital-Lombardi Comprehensive Cancer Center, Washington, DC"}]},{"given":"Erin F.","family":"Cobain","sequence":"additional","affiliation":[{"name":"Rogel Cancer Center, University of Michigan, Ann Arbor, MI"}]},{"given":"Shannon","family":"Puhalla","sequence":"additional","affiliation":[{"name":"University of Pittsburgh, UPMC Hillman Cancer Center, Pittsburgh, PA"}]},{"given":"Rachel","family":"Jankowitz","sequence":"additional","affiliation":[{"name":"University of Pennsylvania, Philadelphia, PA"},{"name":"University of Pittsburgh, UPMC Hillman Cancer Center, Pittsburgh, PA"}]},{"given":"Brent","family":"Rexer","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center, Nashville, TN"}]},{"given":"Ingrid","family":"Mayer","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center, Nashville, TN"}]},{"given":"E. Shelley","family":"Hwang","sequence":"additional","affiliation":[{"name":"Duke University and Duke Cancer Institute, Durham, NC"}]},{"given":"Kimberly","family":"Blackwell","sequence":"additional","affiliation":[{"name":"Duke University and Duke Cancer Institute, Durham, NC"}]},{"given":"Walid","family":"El Ayass","sequence":"additional","affiliation":[{"name":"Tidal Health, Peninsula Regional Medical Center, Salisbury, MD"}]},{"given":"Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Anne Arundel Medical Center, Annapolis, MD"}]},{"given":"Carol","family":"Tweed","sequence":"additional","affiliation":[{"name":"Anne Arundel Medical Center, Annapolis, MD"}]},{"given":"Mary","family":"Wilkinson","sequence":"additional","affiliation":[{"name":"Johns Hopkins University, Baltimore, MD"},{"name":"Inova Schar Cancer, Fairfax, VA"}]},{"given":"Angela","family":"Pennisi","sequence":"additional","affiliation":[{"name":"Inova Schar Cancer, Fairfax, VA"}]},{"given":"Bonnie","family":"Sun","sequence":"additional","affiliation":[{"name":"Johns Hopkins University, Baltimore, MD"}]},{"given":"Pamela","family":"Wright","sequence":"additional","affiliation":[{"name":"Johns Hopkins University, Baltimore, MD"}]},{"given":"Julie R.","family":"Gralow","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Center, University of Washington, Seattle, WA"}]},{"given":"Richard","family":"Chen","sequence":"additional","affiliation":[{"name":"Personalis, Fremont, CA"}]},{"given":"Sean M.","family":"Boyle","sequence":"additional","affiliation":[{"name":"Personalis, Fremont, CA"}]},{"given":"Vered","family":"Stearns","sequence":"additional","affiliation":[{"name":"Johns Hopkins University, Baltimore, MD"}]},{"given":"Antonio C.","family":"Wolff","sequence":"additional","affiliation":[{"name":"Johns Hopkins University, Baltimore, MD"}]},{"given":"Ben Ho","family":"Park","sequence":"additional","affiliation":[{"name":"Vanderbilt 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of Clinical Oncology"],"published-print":{"date-parts":[[2026,5,10]]},"reference-count":20,"published-online":null,"references-count":20,"clinical-trial-number":[{"registry":"10.18810/clinical-trials-gov","clinical-trial-number":"nct02743910"}],"short-container-title":["J Clin Oncol"],"is-referenced-by-count":2},"unpaywall":{"doi":"10.1200/jco-25-02934","is_oa":false,"title":"The Pathologic Response Evaluation and Detection in Circulating Tumor-DNA Study: Ultrasensitive Circulating Tumor-DNA Assessment of Breast Cancer Minimal Residual Disease","updated":"2026-03-12T12:36:34+00:00","published_date":"2026-03-10","best_oa_location":null}},"created_at":"2026-05-10T13:20:49.720Z","updated_at":"2026-05-14T15:13:26.918Z","tags":[{"paper_doi":"10.1200/jco-25-02934","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1200/jco-25-02934","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1200/jco-25-02934","tag_type":"condition","value":"HER2-Positive Breast Cancer","value_numeric":null},{"paper_doi":"10.1200/jco-25-02934","tag_type":"condition","value":"Triple-Negative Breast Cancer","value_numeric":null},{"paper_doi":"10.1200/jco-25-02934","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1200/jco-25-02934","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1200/jco-25-02934","tag_type":"modality","value":"Circulating Tumor DNA (ctDNA) Assay","value_numeric":null},{"paper_doi":"10.1200/jco-25-02934","tag_type":"modality","value":"Minimal Residual Disease Testing","value_numeric":null},{"paper_doi":"10.1200/jco-25-02934","tag_type":"modality","value":"Neoadjuvant Therapy","value_numeric":null},{"paper_doi":"10.1200/jco-25-02934","tag_type":"sample_size","value":"n=220","value_numeric":220},{"paper_doi":"10.1200/jco-25-02934","tag_type":"sex","value":"female","value_numeric":null},{"paper_doi":"10.1200/jco-25-02934","tag_type":"study_design","value":"Prospective Cohort Study","value_numeric":null},{"paper_doi":"10.1200/jco-25-02934","tag_type":"warning","value":"Sex was not explicitly reported in the abstract; 'female' was inferred given the breast cancer population.","value_numeric":null},{"paper_doi":"10.1200/jco-25-02934","tag_type":"warning","value":"The extremely wide confidence interval for post-surgery ctDNA HR (15–1,083) suggests very small event numbers in that subgroup; the point estimate should be interpreted cautiously.","value_numeric":null},{"paper_doi":"10.1200/jco-25-02934","tag_type":"warning","value":"The paper is published in JCO with a listed date of 2026-03-10, which is slightly ahead of today's date (May 10, 2026) — content appears to be a 2026 advance publication and may still be in-press or recently published.","value_numeric":null},{"paper_doi":"10.1200/jco-25-02934","tag_type":"warning","value":"The prespecified secondary IDFS endpoint was defined only for the TNBC cohort; prognostic data reported for the combined HER2-positive and TNBC population should be interpreted with caution regarding generalizability.","value_numeric":null}],"summaries":{"what_studied":"Prospective multicenter study (PREDICT ctDNA) evaluating an ultrasensitive, tumor-informed ctDNA assay (<100 ppm) as a biomarker of minimal residual disease in 220 evaluable patients with stage II/III HER2-positive or TNBC receiving neoadjuvant therapy (NAT), with ctDNA measured at baseline, post-NAT, and post-surgery; primary endpoint was NPV of post-NAT ctDNA for pCR ≥90%, and a prespecified secondary endpoint assessed ctDNA vs. 5-year invasive disease-free survival (IDFS) in the TNBC cohort.","key_result":"Primary objective not met: post-NAT ctDNA NPV for pCR was only 60% (95% CI, 0.50–0.69), as 40% of non-pCR patients were ctDNA-negative. However, detectable ctDNA after NAT strongly predicted recurrence (HR 8.9, 95% CI 2.4–33; P=.001), and detectable ctDNA after surgery conferred extreme recurrence risk (HR 128, 95% CI 15–1,083; P<.001); ctDNA-negative patients post-surgery achieved 94% 5-year IDFS.","limitations":"- TNBC and HER2-positive cohorts were analyzed together for the primary endpoint, which may mask subgroup differences.\n- The secondary IDFS endpoint was prespecified only for the TNBC cohort, limiting generalizability of prognostic findings to HER2-positive disease.\n- Relatively small sample size (n=220 evaluable) may limit precision of high-risk subgroup estimates, as reflected by the very wide CI for post-surgery HR (15–1,083).","practice_takeaway":"Post-NAT ctDNA cannot replace pathologic assessment for confirming pCR, but a positive ctDNA result after NAT or surgery flags patients at markedly elevated recurrence risk who may benefit from treatment escalation. ctDNA-negative status after surgery identifies a low-risk group (94% 5-year IDFS) where de-escalation strategies could be considered."}},{"doi":"10.1200/jco-25-02855","pmid":"41576311","title":"Rise and Fall of Neoadjuvant Carboplatin for Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer","journal_title":"Journal of Clinical Oncology","journal_issn":"0732-183X","published_at":"2026-01-23T00:00:00.000Z","url":"https://doi.org/10.1200/jco-25-02855","source_score":63,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-05T13:38:52.408Z","updated_at":"2026-07-05T13:38:52.408Z","tags":[{"paper_doi":"10.1200/jco-25-02855","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1200/jco-25-02855","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1200/jco-25-02855","tag_type":"condition","value":"HER2-Positive Breast Cancer","value_numeric":null},{"paper_doi":"10.1200/jco-25-02855","tag_type":"generic","value":"carboplatin","value_numeric":null},{"paper_doi":"10.1200/jco-25-02855","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1200/jco-25-02855","tag_type":"level_of_evidence","value":"7","value_numeric":null},{"paper_doi":"10.1200/jco-25-02855","tag_type":"modality","value":"Anti-HER2 Therapy","value_numeric":null},{"paper_doi":"10.1200/jco-25-02855","tag_type":"modality","value":"Platinum-Based Chemotherapy","value_numeric":null},{"paper_doi":"10.1200/jco-25-02855","tag_type":"study_design","value":"Editorial / Perspective","value_numeric":null},{"paper_doi":"10.1200/jco-25-02855","tag_type":"warning","value":"Sex tag omitted as the paper does not explicitly report sex distribution of the studied population in the available metadata.","value_numeric":null},{"paper_doi":"10.1200/jco-25-02855","tag_type":"warning","value":"The 'practice_changing' impact flag reflects the paper's argument that carboplatin's routine use is being reconsidered, not a new positive recommendation for its adoption.","value_numeric":null},{"paper_doi":"10.1200/jco-25-02855","tag_type":"warning","value":"This appears to be an editorial or perspective article, not a primary clinical trial — no patient-level data, sample sizes, or direct effect sizes could be extracted. Summary content reflects the described narrative and conclusions.","value_numeric":null}],"summaries":{"what_studied":"This paper examines the trajectory of neoadjuvant carboplatin use in HER2-positive breast cancer, evaluating its role in improving pathologic complete response (pCR) rates and long-term outcomes when added to standard HER2-directed therapy.","key_result":"While carboplatin addition to neoadjuvant regimens improved pCR rates in HER2-positive breast cancer, evidence for a corresponding long-term survival benefit has not been firmly established, contributing to a reassessment of its routine use.","limitations":"The paper is a perspective/commentary piece rather than a primary trial, limiting direct extraction of patient-level data, effect sizes, or confidence intervals from a single controlled study.","practice_takeaway":"Clinicians should weigh the incremental pCR gains from adding carboplatin to neoadjuvant HER2-directed regimens against increased toxicity, given the lack of clear long-term survival benefit. Routine use of carboplatin in this setting is under scrutiny and may not be warranted for all HER2-positive patients."}},{"doi":"10.1158/1078-0432.ccr-25-2882","pmid":"41335375","title":"Palbociclib, Trastuzumab, and Endocrine Therapy in Pretreated HER2-Positive and PAM50 Luminal Advanced Breast Cancer: Randomized Phase II, SOLTI-1303 PATRICIA Trial","journal_title":"Clinical Cancer Research","journal_issn":"1078-0432","published_at":"2025-12-03T00:00:00.000Z","url":"https://doi.org/10.1158/1078-0432.ccr-25-2882","source_score":77,"is_retracted":false,"is_open_access":false,"raw_metadata":{"ooir":{"day":"2026-01-08","doi":"10.1158/1078-0432.ccr-25-2882","days":"14","issn":"1078-0432","rank":"10","field":"Clinical Medicine","score":"77","category":"Oncology","categories":["Oncology"],"_categories":["Oncology"]},"pubmed":{"doi":"10.1158/1078-0432.CCR-25-2882","title":"Palbociclib, trastuzumab and endocrine therapy in pretreated HER2-positive and PAM50 luminal advanced breast cancer: randomised phase II, SOLTI-1303 PATRICIA trial.","journal":"Clinical cancer research : an official journal of the American Association for Cancer Research","methods":"","results":"264 participants were pre-screened between August 2019-2023, and 73 patients were randomised (including seven re-randomisations). In the TPC arm: 48.5% were treated with trastuzumab plus chemotherapy, 39.4% with T-DM1 and 12.1 % with trastuzumab plus ET. The triplet was associated with a significantly better PFS compared to TPC (stratified hazard ratio=0.52 [95% CI 0.29-0.95]; two-sided p=0.03). PFS rates after 24 months were 24.0% with the triplet and 4.3% in the TPC arm. The overall response rate was 18.9% (95% CI 8.6-35.7) and 7.1% (95% CI 1.2-25.0), respectively. In the triplet arm, grade ≥3 adverse events occurred in 61.5% of patients, with neutropenia being the most frequent (53.9%). No permanent discontinuations due to toxicity were observed.","abstract":"$32","keywords":[],"pubmed_id":"41335375","conclusions":"","publication_date":"2025-12-03T00:00:00"},"crossref":{"DOI":"10.1158/1078-0432.ccr-25-2882","URL":"https://doi.org/10.1158/1078-0432.ccr-25-2882","ISSN":["1078-0432","1557-3265"],"link":[{"URL":"https://aacrjournals.org/clincancerres/article-pdf/doi/10.1158/1078-0432.CCR-25-2882/3708870/ccr-25-2882.pdf","content-type":"application/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https://aacrjournals.org/clincancerres/article-pdf/doi/10.1158/1078-0432.CCR-25-2882/3723636/ccr-25-2882.pdf","content-type":"application/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https://aacrjournals.org/clincancerres/article-pdf/doi/10.1158/1078-0432.CCR-25-2882/3723636/ccr-25-2882.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":"OF1-OF10","type":"journal-article","issue":null,"score":1,"title":["Palbociclib, Trastuzumab, and Endocrine Therapy in Pretreated HER2-Positive and PAM50 Luminal Advanced Breast Cancer: Randomized Phase II, SOLTI-1303 PATRICIA Trial"],"author":[{"given":"Eva","family":"Ciruelos","sequence":"first","affiliation":[{"name":"1SOLTI Cancer Research Group, Barcelona, Spain."},{"name":"2Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain."},{"name":"3HM Hospitales, Madrid, Spain."}]},{"given":"Tomás","family":"Pascual","sequence":"additional","affiliation":[{"name":"1SOLTI Cancer Research Group, Barcelona, Spain."},{"name":"4Medical Oncology, Institute of Cancer and Blood Diseases, Hospital Clinic of Barcelona, Barcelona, Spain."},{"name":"5Translational Genomics and Targeted Therapies in Solid Tumors group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain."},{"name":"6Faculty of Biomedical and Health Sciences, Department of Medicine, Universidad Europea de Madrid, Madrid, Spain."}]},{"given":"Guillermo","family":"Villacampa","sequence":"additional","affiliation":[{"name":"1SOLTI Cancer Research Group, Barcelona, Spain."},{"name":"7Statistics Unit, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain."}]},{"given":"Sonia","family":"Pernas","sequence":"additional","affiliation":[{"name":"1SOLTI Cancer Research Group, Barcelona, Spain."},{"name":"8Medical Oncology Department, Institut Catala d’ Oncologia (ICO)- Institute of Biomedical Research of Bellvitge (IDIBELL), L’Hospitalet del Llobregat, Barcelona, Spain."}]},{"given":"Rodrigo","family":"Sanchez-Bayona","sequence":"additional","affiliation":[{"name":"1SOLTI Cancer Research Group, Barcelona, Spain."},{"name":"2Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain."}]},{"given":"José","family":"Ponce","sequence":"additional","affiliation":[{"name":"9Medical Oncology, Hospital General Universitario Dr. Balmis, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, Spain."},{"name":"10GEICAM Spanish Breast Cancer Group, Madrid, Spain."}]},{"given":"Blanca","family":"Cantos","sequence":"additional","affiliation":[{"name":"11Hospital Universitario Puerta de Hierro, Madrid, Spain."}]},{"given":"Santiago","family":"Escrivá-de-Romaní","sequence":"additional","affiliation":[{"name":"12Medical Oncology Department, Vall d’Hebron University Hospital, and Breast Cancer Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain."}]},{"given":"Antonia","family":"Perelló","sequence":"additional","affiliation":[{"name":"13Medical Oncology Department, Hospital Universitario Son Espases, Palma De Mallorca, Spain."}]},{"given":"Esther","family":"Sanfeliu","sequence":"additional","affiliation":[{"name":"1SOLTI Cancer Research Group, Barcelona, Spain."},{"name":"5Translational Genomics and Targeted Therapies in Solid Tumors group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain."},{"name":"14Pathology Department, Hospital Clínic de Barcelona, Barcelona, Spain."}]},{"given":"Patricia","family":"Galvan","sequence":"additional","affiliation":[{"name":"5Translational Genomics and Targeted Therapies in Solid Tumors group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain."}]},{"given":"Alvaro","family":"Montaño","sequence":"additional","affiliation":[{"name":"15Department of Medical Oncology, Hospital Universitario Virgen del Rocío, Sevilla, Spain."}]},{"given":"Eduardo","family":"Martínez","sequence":"additional","affiliation":[{"name":"16Consorcio Hospitalario Provincial de Castellón, Castellón de la Plana, Spain."}]},{"given":"Ana","family":"Lopez","sequence":"additional","affiliation":[{"name":"10GEICAM Spanish Breast Cancer Group, Madrid, Spain."},{"name":"17Complejo Asistencial Universitario de León, León, Spain."}]},{"given":"Mireia","family":"Mele","sequence":"additional","affiliation":[{"name":"18Medical Oncology, Hospital Universitari Sant Joan de Reus, Reus, Spain."}]},{"given":"Juan","family":"de la Haba","sequence":"additional","affiliation":[{"name":"10GEICAM Spanish Breast Cancer Group, Madrid, Spain."},{"name":"19Medical Oncology Department, Hospital Universitario Reina Sofia, Cordoba, Spain."}]},{"given":"Javier","family":"Cortés","sequence":"additional","affiliation":[{"name":"6Faculty of Biomedical and Health Sciences, Department of Medicine, Universidad Europea de Madrid, Madrid, Spain."},{"name":"20International Breast Cancer Center (IBCC), Pangaea Oncology, Quironsalud Group, Barcelona, Spain."},{"name":"21IOB Madrid, Hospital Beata Maria Ana, Madrid, Spain."}]},{"given":"Antonio","family":"Mulero-Sánchez","sequence":"additional","affiliation":[{"name":"1SOLTI Cancer Research Group, Barcelona, Spain."}]},{"given":"Juan M.","family":"Ferrero-Cafiero","sequence":"additional","affiliation":[{"name":"1SOLTI Cancer Research Group, Barcelona, Spain."}]},{"given":"Mafalda","family":"Oliveira","sequence":"additional","affiliation":[{"name":"1SOLTI Cancer Research Group, Barcelona, Spain."},{"name":"12Medical Oncology Department, Vall d’Hebron University Hospital, and Breast Cancer Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain."}]},{"given":"Lorea","family":"Villanueva","sequence":"additional","affiliation":[{"name":"1SOLTI Cancer Research Group, Barcelona, Spain."}]},{"given":"Xavier","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"1SOLTI Cancer Research Group, Barcelona, Spain."},{"name":"22Medical Oncology, IOR - Instituto Oncologico Dr. Rosell, Hospital General de Catalunya, Barcelona, Spain."}]},{"given":"Patricia","family":"Villagrasa","sequence":"additional","affiliation":[{"name":"1SOLTI Cancer Research Group, Barcelona, Spain."},{"name":"23Reveal Genomics, S.L Barcelona, Barcelona, Spain."}]},{"given":"Aleix","family":"Prat","sequence":"additional","affiliation":[{"name":"1SOLTI Cancer Research Group, Barcelona, Spain."},{"name":"4Medical Oncology, Institute of Cancer and Blood Diseases, Hospital Clinic of Barcelona, Barcelona, Spain."},{"name":"5Translational Genomics and Targeted Therapies in Solid Tumors group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain."},{"name":"23Reveal Genomics, S.L Barcelona, Barcelona, Spain."}]}],"funder":[{"id":[{"id":"10.13039/100004319","id-type":"DOI","asserted-by":"publisher"}],"DOI":"10.13039/100004319","name":"Pfizer","doi-asserted-by":"publisher"}],"issued":{"date-parts":[[2026,1,6]]},"member":"1086","prefix":"10.1158","source":"Crossref","volume":null,"created":{"date-time":"2025-12-03T16:04:32Z","timestamp":1764777872000,"date-parts":[[2025,12,3]]},"indexed":{"date-time":"2026-01-06T16:31:26Z","timestamp":1767717086180,"date-parts":[[2026,1,6]]},"subject":[],"abstract":"$33","language":"en","relation":{},"resource":{"primary":{"URL":"https://aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-25-2882/771469/Palbociclib-Trastuzumab-and-Endocrine-Therapy-in"}},"subtitle":[],"deposited":{"date-time":"2026-01-06T16:28:49Z","timestamp":1767716929000,"date-parts":[[2026,1,6]]},"issn-type":[{"type":"print","value":"1078-0432"},{"type":"electronic","value":"1557-3265"}],"published":{"date-parts":[[2026,1,6]]},"publisher":"American Association for Cancer Research (AACR)","reference":null,"short-title":[],"update-policy":"https://doi.org/10.1158/crossmark_policy","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"original-title":[],"container-title":["Clinical Cancer Research"],"reference-count":0,"published-online":{"date-time":null,"timestamp":null,"date-parts":[[2026,1,6]]},"references-count":0,"short-container-title":[],"is-referenced-by-count":0},"unpaywall":{"doi":"10.1158/1078-0432.ccr-25-2882","is_oa":false,"title":"Palbociclib, Trastuzumab, and Endocrine Therapy in Pretreated HER2-Positive and PAM50 Luminal Advanced Breast Cancer: Randomized Phase II, SOLTI-1303 PATRICIA Trial","updated":"2026-01-10T04:46:20+00:00","published_date":"2025-12-03","best_oa_location":null}},"created_at":"2026-01-11T11:19:33.869Z","updated_at":"2026-01-17T09:03:27.421Z","tags":[{"paper_doi":"10.1158/1078-0432.ccr-25-2882","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-2882","tag_type":"condition","value":"HER2-Positive Breast Cancer","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-2882","tag_type":"generic","value":"palbociclib","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-2882","tag_type":"generic","value":"trastuzumab","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-2882","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-2882","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-2882","tag_type":"modality","value":"CDK4/6 Inhibitor","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-2882","tag_type":"modality","value":"Endocrine Therapy","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-2882","tag_type":"modality","value":"HER2-Targeted Therapy","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-2882","tag_type":"sample_size","value":"n=73","value_numeric":73},{"paper_doi":"10.1158/1078-0432.ccr-25-2882","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-2882","tag_type":"warning","value":"Comparator arm consisted of heterogeneous regimens (trastuzumab + chemotherapy, T-DM1, or trastuzumab + endocrine therapy).","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-2882","tag_type":"warning","value":"Only investigator-assessed PFS is reported; no OS data provided.","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-2882","tag_type":"warning","value":"Open-label phase II randomized design with small N and re-randomization in the physician’s choice arm may affect interpretation.","value_numeric":null}],"summaries":{"what_studied":"A multicenter, open-label, randomized phase II trial compared palbociclib + trastuzumab + endocrine therapy with trastuzumab-based treatment of physician’s choice in pretreated HER2-positive, HR-positive, PAM50-luminal A/B advanced breast cancer; the primary endpoint was investigator-assessed PFS per RECIST 1.1. From August 2019–2023, 264 were pre-screened and 73 were randomized (including 7 re-randomizations).","key_result":"The triplet improved PFS versus physician’s choice (HR 0.52, 95% CI 0.29–0.95; p=0.03); 24-month PFS rates were 24.0% with the triplet and 4.3% with physician’s choice. ORR was 18.9% (95% CI 8.6–35.7) for the triplet versus 7.1% (95% CI 1.2–25.0), and in the triplet arm grade ≥3 AEs occurred in 61.5% with neutropenia in 53.9% and no permanent discontinuations due to toxicity.","limitations":"Open-label phase II study with a small randomized sample (n=73) and allowance for re-randomization in the physician’s choice arm. The comparator was heterogeneous (trastuzumab + chemotherapy, T-DM1, or trastuzumab + endocrine therapy), and outcomes were investigator-assessed.","practice_takeaway":"In selected pretreated HR+/HER2+ PAM50-luminal A/B advanced breast cancer, adding palbociclib to trastuzumab and endocrine therapy prolonged PFS versus trastuzumab-based options. Expect frequent neutropenia; monitor counts, noting no permanent discontinuations were reported."}}],"initialOffset":12,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"condition","value":"HER2-Positive Breast Cancer"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Conditions","href":"/hub/tag/condition"},{"name":"HER2-Positive Breast Cancer"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"condition","hub_tag_value":"HER2-Positive Breast Cancer"}}}]]

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