tbuckley/cabot-search huggingface dataset:
Trends and outcomes in patients receiving neoadjuvant chemotherapy for breast cancer in Ontario: A population-based study.
Authors: Matthew Castelo, Lena Nguyen, Amanda Roberts
Journal: Journal of Clinical Oncology (2024)

e12664 Background: Modern neoadjuvant chemotherapy (NAC) regimens in breast cancer offer higher rates of pathologic complete response, an ability to guide further adjuvant treatment, and may de-escalate surgery. However, the utilization of NAC has been heterogeneous in Ontario. This study aimed to describe trends in NAC use in Ontario, report survival outcomes, and explore factors associated with overall survival in these patients. Methods: This was a population-based cohort study using linked health administrative data in Ontario, Canada. From the Ontario Cancer Registry, we identified women ≥18 years who underwent neoadjuvant chemotherapy followed by surgery for operable (cT1N1, cT2-3N0, or cT2-3N1) breast cancer between 2012 and 2020. Patients were divided by receptor subtype (triple negative breast cancer [TNBC], ER+/HER2-, ER+/HER2+, ER-/HER2+) and characteristics were compared using standardized mean differences (SMDs). Five-year overall survival (OS) and breast cancer-specific survival (BCSS) were determined and reported for each subtype. Associations with OS and BCSS were calculated for patient and disease characteristics using univariate and multivariable Cox proportional hazards models and Fine and Gray models, respectively. Results: 3,804 women underwent NAC for cT1N1, cT2-3N0, or cT2-3N1 breast cancer in Ontario between 2012 and 2020. The largest contributing subtype was ER+/HER2- patients (39.3%) followed by those with HER2+ disease (ER-/HER2+ 13.8%, ER+/HER2+ 23.4%), and TNBC (23.5%). The median age was 50 years (IQR 42-59 years). Most patients were clinically node-positive (2,736; 71.9%), and underwent mastectomy (2,397; 63.0%). There was a significant increase in the number of patients receiving NAC in Ontario, from 217 in 2012 to 667 in 2019 ( p&lt;0.001), with a greater increase among patients with TNBC or HER2+ disease. Compared to those with ER+/HER2- disease, TNBC patients were treated for smaller tumours (28.6% T3 vs. 39.8%; SMD = 0.24), and were more likely to be node-negative (39.1% N0 vs. 22.1%; SMD = 0.38). Similar trends for nodal status were found for patients with ER-/HER2+ (26.7% N0) and ER+/HER2+ cancer (27.9% N0). 5-year OS for the entire cohort was 88.1% (95% CI 87.1 – 89.2%). Survival was highest for ER+/HER2+ patients (94.2%, 95% CI 92.6 – 95.8%) and lowest for TNBC patients (80.1%, 95% CI 77.5 – 82.8%). Similar patterns were seen for BCSS. Factors associated with OS in a multivariable model included older age (increase in 5 years HR 1.1, 95% CI 1.07 – 1.14), N1 status (HR 1.99, 95% CI 1.61 – 2.47), larger tumour size (T3 HR 1.83, 95% CI 1.34 – 2.5), mastectomy (HR 1.45, 95% CI 1.2 – 1.75), and TNBC (versus ER+/HER2- HR 1.9, 95% CI 1.56 – 2.32). Conclusions: The use of NAC has increased in Ontario, particularly among TNBC and HER2+ patients. Women with TNBC have worse outcomes compared to those with ER+/HER2- disease, despite being treated for less advanced disease.
Phase III study to evaluate the efficacy and safety of GLSI-100 (GP2 + GM-CSF) in patients with breast cancer with residual disease or high-risk PCR after both neo-adjuvant and postoperative adjuvant anti-HER2 therapy: Flamingo-01.
Authors: Snehal Patel, Jaye Thompson, Mira Patel, F. Joseph Daugherty, Mothaffar F. Rimawi
Journal: Journal of Clinical Oncology (2024)

TPS617 Background: GP2 is a biologic nine amino acid peptide of the HER2/ neu protein delivered in combination with Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) that stimulates an immune response targeting HER2/neu expressing cancers, the combination known as GLSI-100. Of the 146 patients that have been treated with GLSI-100 over 4 clinical trials, GLSI-100 was well-tolerated and no serious adverse events observed were considered related to the immunotherapy. Methods: This Phase III trial is a prospective, randomized, double-blinded, multi-center study. After 1 year of trastuzumab-based therapy, 6 intradermal injections of GLSI-100 or placebo will be administered over the first 6 months and 5 subsequent boosters will be administered over the next 2.5 years for a total of 11 injections over 3 years. The participant duration of the trial will be 3 years treatment plus 1 additional year follow-up for a total of 4 years following the first year of treatment with trastuzumab-based therapy. Patients will be stratified based on residual disease status at surgery, hormone receptor status and region. Study size, interim analysis: Approximately 498 patients will be enrolled. To detect a hazard ratio of 0.3 in invasive breast cancer free survival (IBCFS), 28 events will be required. An interim analysis for superiority and futility will be conducted when at least 14 events have occurred. This sample size provides 80% power if the annual rate of events in placebo patients is 2.4% or greater. Up to 100 non-HLA-A*02 subjects will be enrolled in an open-label arm. The patient population is defined by these key eligibility criteria: HER2/neu positive and HLA-A*02; residual disease or high risk pCR (Stage III at presentation) post neo-adjuvant therapy; exclude Stage IV; completed at least 90% of planned trastuzumab-based therapy. Trial objectives: To determine if GP2 therapy increases IBCFS; to assess the safety profile of GP2; and to monitor immunologic responses to treatment and assess relationship to efficacy and safety. Study status: The study has been initiated at a number of sites in the US. The study is also expected to be opened in Spain, France, Germany, Italy, and Poland. Clinical trial information: NCT05232916 .
Memory mayhem: Hormone therapy causing brain fog in patients with DCIS.
Authors: Devashish Desai, Prashanth Ashok Kumar, Sam Benjamin
Journal: Journal of Clinical Oncology (2024)

575 Background: Long term hormonal therapy in ductal carcinoma in situ (DCIS) have been studied without consistent evidence to cause cognitive side effects. Here we evaluate the relation of using hormonal therapy (HT) in patients with DCIS with cognitive effects. Methods: TrinetX, a global federated research network that provides a dataset of electronic medical records from different healthcare organizations (HCOs), was utilized. Initial query was made to isolate patients who had an ER positive DCIS. Two groups were made based on the receipt of hormone therapy (exemestane, tamoxifen, letrozole, anastrozole). Further, propensity score matching (PSM) was carried out to match age, sex, race, development of malignant neoplasm of breast, chemotherapy at any point. Outcomes of cognitive impairment were identified using ICD 10 CM codes R41.3, R41.0, F05, F02.81, and Alzheimer’s dementia was identified using ICD 10 CM code G30. Compare outcome analytic function was utilized to map the co-relation of HT with cognitive impairment. Results: 64,266 patients were identified with ER positive DCIS, of whom 63.18% (n=40,601) received HT. Patients who received HT were older (61.4 ± 12.3 vs. 61 ± 12.9, p&lt;0.0001), and predominantly Caucasian (70% vs 65%, p&lt;0.0001). On looking further into racial distribution of population, it was seen that Caucasians were predominant in both groups, followed by African Americans (12% vs. 11%, p=0.0016) and Unknown race (11% vs. 17%, p&lt;0.0001), then Asians (4% vs. 4%, p=0.0675). Before PSM, it was seen that 7.55% (n= 2,818) patients had cognitive side effects compared to only 5.044% (n= 1,139) in group that did not receive HT (OR 1.537 (1.432,1.65), p&lt;0.0001). Log-Rank Test for Kaplan-Meier curve was significant for the difference with hazard ratio 1.315, (1.227,1.409). A similar association was seen with Alzheimer’s dementia (0.735% vs. 0.547%, OR 1.346 (1.094,1.656), p= 0.0048) but Kaplan-Meier survival analysis did not show any significant difference between the groups. After PSM, both groups had 15,801 cases. The odds of developing cognitive impairment was higher in HT group (6.582% vs. 5.589%, OR 1.19, (1.082,1.309), p=0.0003). But Log-Rank Test for Kaplan-Meier curve did not show any significant difference (HR 1.047 (95% CI 0.954-1.149)). There was no significant difference for Alzheimer’s dementia development in either group (0.769% vs. 0.591%, 1.303 (0.994,1.709), p = 0.0548). Conclusions: Our study shows that HT significantly increases the odds of developing cognitive impairment. The limitation of the study is the duration of follow up. Usually, patients with DCIS live much longer and can have cognitive effects beyond the window of this study; hence a prospective long-term follow-up study is required to ascertain the relation of HT and cognitive side effects. Patients when starting the treatment should be counselled about the risk of developing cognitive side effects in future.
Comparing <sup>18</sup>F-FDG positron emission tomography (PET) and breast magnetic resonance imaging (MRI) to predict pathological complete response (pCR) and 3-year invasive disease-free survival (3-y iDFS) in patients (pts) with HER2+ early breast cancer (EBC): An unplanned exploratory analysis of PHERGain trial.
Authors: José Manuel Pérez García, Javier Cortes, Manuel Ruiz-Borrego, Agostina Stradella, Begoña Bermejo, Santiago Escrivá-de-Romaní, Lourdes Calvo, Geraldine Gebhart, Khaldoun Kerrou, Juan José García-Mosquera, Maria Gion, Gabriele Antonarelli, Laura López-Montero, José Rodríguez-Morató, Leonardo Mina, Miguel Sampayo-Cordero, Antonio Llombart-Cussac
Journal: Journal of Clinical Oncology (2024)

586 Background: The PHERGain phase II trial (1) (NCT03161353) demonstrated the feasibility of chemotherapy (CT)-free treatment using a PET-based, pCR-adapted strategy in HER2+ EBC pts treated with dual HER2 blockade (trastuzumab pertuzumab; HP). Due to limited PET availability, breast MRI is warranted as an alternative tool for assessing early treatment response. Methods: Briefly, group B pts in PHERGain were initially treated with HP, and CT was subsequently introduced according to on-treatment PET results. Adjuvant therapy was determined based on prior neoadjuvant treatment (NAT) and pCR. All pts completed up to 18 HP cycles. PET and MRI were performed before randomization and after 2 treatment cycles, with an additional MRI performed before surgery. PET response was centrally assessed per EORTC criteria. Locally assessed MRI response was defined as a ≥30% decrease in the sum of diameters of the target lesions. MRI reduction was defined ad hoc as any shrinkage in the diameter of target lesions after 2 cycles without new lesions or progressive disease in non-target lesions. Results: After 2 HP cycles, 79.6% (227/285) of group B pts were PET responders, 47% (134/285) had an MRI response, and 82.5% (235/285) achieved an MRI reduction. A high association was observed between PET response and MRI reduction. Similar rates of pCR and 3-y iDFS were observed between pts with a PET response or an MRI reduction. PET-nonresponders without MRI reduction had the worst 3-y iDFS despite receiving standard NAT with CT and HP (Table). Conclusions: The complex design of this study does not allow a direct comparison between PET and MRI. Although PET is the recommended imaging technique for early treatment response, these data suggest that MRI-assessed tumor shrinkage could alternatively guide NAT after the first 2 HP cycles in HER2+ EBC pts following the PHERGain strategy when PET is not available. 1. Pérez-García JM, Lancet Oncol 2021. Clinical trial information: NCT03161353 . [Table: see text]
Telisotuzumab vedotin monotherapy in patients with previously treated c-Met–overexpressing non-squamous <i>EGFR</i> wildtype advanced NSCLC: Primary analysis of the LUMINOSITY trial.
Authors: David Ross Camidge, Jair Bar, Hidehito Horinouchi, Jonathan W. Goldman, Fedor Vladimirovich Moiseenko, Elena Filippova, Irfan Cicin, Tudor Eliade Ciuleanu, Nathalie Daaboul, Chunling Liu, Penelope Ann Bradbury, Mor Moskovitz, Nuran Katgi, Pascale Tomasini, Alona Zer, Jim Looman, Christine Ratajczak, Martha Li, Summer Xia, Shun Lu
Journal: Journal of Clinical Oncology (2024)

103 Background: Approximately 25% of patients (pts) with non-squamous (NSQ) EGFR wildtype (WT) NSCLC have c-Met protein overexpression (Ansell et al. 2022 CRUK), which is associated with a poor prognosis (Liang, Wang. Onco Targets Ther. 2020). Telisotuzumab vedotin (Teliso-V) is a c-Met–directed antibody-drug conjugate comprising the mAb telisotuzumab and the microtubule polymerization inhibitor monomethyl auristatin E. The phase 2 LUMINOSITY trial (NCT03539536) aimed to identify the c-Met–overexpressing (OE) NSCLC population best suited to Teliso-V and expand selected group(s) for further evaluation of efficacy. We report on the primary analysis for pts with c-Met OE NSQ EGFRWT NSCLC. Methods: This phase 2, non-randomized, multicenter study enrolled pts with locally advanced/metastatic c-Met OE NSCLC, ≤2 prior lines of therapy (chemotherapy [CTx] + immunotherapy [IO] or sequential CTx + IO), and ≤1 line of chemotherapy. c-Met OE (Ventana MET [SP44] clinical trial assay [CTA]) was defined as ≥25% tumor cells with 3+ staining (high: ≥50% 3+; intermediate [int]: 25 to &lt;50% 3+). Teliso-V was dosed at 1.9 mg/kg IV Q2W. Primary endpoint was overall response rate (ORR) by independent central review per RECIST v1.1. Results: 172 pts with NSQ EGFR WT NSCLC received ≥1 dose of Teliso-V and comprised the safety population; 161 (c-Met high, 78; c-Met int, 83) were included in baseline and efficacy analyses. Median age was 64 yrs (range 33–83), 69% were male, and 70% had ECOG PS 1. 97.5% had prior platinum and 82.0% had prior immune checkpoint inhibitor. Efficacy data are presented in Table below. ORR was 34.6% (c-Met high), 22.9% (c-Met int), 28.6% (overall). Median DOR was 9.0 mo (c-Met high), 7.2 mo (c-Met int), 8.3 mo (overall). Most common any-grade treatment-related AEs (TRAEs) were peripheral sensory neuropathy (30%), peripheral edema (16%), and fatigue (14%). Grade 5 TRAEs occurred in 2 pts (interstitial lung disease, respiratory failure). Conclusions: Teliso-V has shown compelling and durable responses in pts with c-Met OE NSQ EGFR WT NSCLC, especially in pts with c-Met high. Teliso-V had an acceptable safety profile that was clinically manageable, which is consistent with previous data. Clinical trial information: NCT03539536 . [Table: see text]
Association of tumor-infiltrating lymphocytes (TILs) and immune signatures with PAM50 intrinsic subtyping hormone receptor-positive (HR+)/HER2-negative (HER2-) early breast cancer (BC): A translational analysis of two multicentric neoadjuvant trials.
Authors: Gaia Griguolo, Laia Paré, Federica Miglietta, Michele Bottosso, Daniele Giulio Generali, Antonio Frassoldati, Antonino Musolino, Simon Spazzapan, Grazia Vernaci, Tommaso Giarratano, Rocco Cappellesso, Giancarlo Bisagni, Federico Piacentini, Enrico Tagliafico, Katia Cagossi, Claudia Pinato, Francesca Schiavi, Aleix Prat, Maria Vittoria Dieci, Valentina Guarneri
Journal: Journal of Clinical Oncology (2024)

558 Background: HR+/HER2− BCs are generally described as immunologically cold, with low levels of TILs and PD-L1. Nevertheless, the addition of immunotherapy (ICI) to chemo has been reported to increase pCR rates in high-risk early HR+/HER2– BCs. Assessing the interaction between immune features and tumor biology may identify of a subset of patients (pts) with HR+/HER2− BC that would be the ideal candidates for the combination of chemo and ICI. Methods: Gene-expression data from two multicentric neoadjuvant phase II trials (GIADA, LETLOB) enrolling stage II-IIIA HR+HER2- BC pts was retrieved (Dieci, CCR 2022; Guarneri, JCO 2014). In the GIADA trial, 758 genes were assessed on baseline tumor samples by nCounter (N=43). In the LETLOB trial, gene-expression data (Affymetrix platform) from baseline core-biopsies was available for 66 pts. Intrinsic subtype was assigned using a research-based PAM50 predictor. TILs were evaluated following guidelines. Association of TILs and immune signatures with intrinsic subtyping was assessed by Kruskal-Wallis test. Results: PAM50 subtype distribution (N=109) was 44% Luminal B (LumB), 33% Luminal A (LumA), 18% Basal-like, 5% HER2-enriched (HER2-E). TILs were assessed on 101 samples: median 2 (range 0-100). Basal-like BCs showed higher TILs than other subtypes (p=0.008). No significant difference was observed between LumA and LumB BCs (Table). Basal-like tumors showed higher levels of previously published immune signatures associated with CD8 T-cells (p&lt;0.001), Cytotoxic cells (p&lt;0.001), IFN-gamma (p&lt;0.001), and response to ICI in the GeparNuevo trial (p=0.003) (N=109). PD-1 (p=0.002), PD-L1 (p=0.001), and PD-L2 (p=0.001) genes were also more expressed in Basal-like BCs (evaluable in 43 samples). No significant difference was observed between LumA and LumB tumors. A significant weak to moderate positive correlation was observed between continuous TILs and immune signatures and basal-like PAM50 signature (p&lt;0.001, Spearman coefficient=0.372 for TILs, from 0.354 to 0.648 for immune signatures). Conclusions: PAM50 intrinsic subtyping and TILs/immune signatures capture only partially overlapping information on the biology of HR+/HER2- BCs. Pts with HR+/HER2- BCs simultaneously showing features of biological aggressiveness and enhanced immunogenicity may represent the ideal candidates for the combination of ICI and chemo. [Table: see text]
Pathological complete response (pCR) association with a novel homologous recombination deficiency HRD signature (HRDsig) in patients with triple-negative breast cancer (TNBC) receiving neoadjuvant therapy (Tx).
Authors: Tanya Gupta, Ryon P Graf, Alexa B. Schrock, Russell Madison, Jeffrey S. Ross, Mia Alyce Levy, Julia Quintanilha
Journal: Journal of Clinical Oncology (2024)

591 Background: The current standard of care for stage II-III TNBC is neoadjuvant Tx combining carboplatin, paclitaxel, and immune checkpoint inhibitor (ICI) followed by doxorubicin and cyclophosphamide (AC) + ICI. This regimen is often associated with significant toxicity. This study aimed to investigate if HRDsig could identify patients with TNBC who have a greater benefit from the addition of platinum in the neoadjuvant Tx regimen. Methods: This study included patients with TNBC who underwent genomic testing using Foundation Medicine tissue comprehensive genomic profiling (CGP) assays and had records of neoadjuvant Tx. Patient clinical data was obtained by the US-wide de-identified Flatiron Health and Foundation Medicine real-world clinicogenomic breast cancer database (CGDB), originated from ~280 US cancer clinics between January 2011 and June 2023. pCR rates were compared between patients HRDsig(+) vs. HRDsig(-) who were stratified by having received platinum vs. non-platinum Tx and between patients receiving non-platinum vs. platinum neoadjuvant Tx stratified by HRDsig status. The interaction effect of HRDsig and platinum Tx in relation to pCR was evaluated by logistic regression. Results: 497 patients met the inclusion criteria, 159 (32%) with HRDsig(+) and 338 (68%) with HRDsig(-). Among HRDsig(+) patients, 54 (34%) received platinum and 105 (66%) non-platinum Tx. HRDsig(+) vs. HRDsig(-) patients were more likely to have pCR receiving both platinum Tx (37.0% vs. 4.4%, p&lt;0.001) and non-platinum Tx (23.8% vs. 5.2%, p&lt;0.001). Platinum vs. non-platinum Tx showed a trend towards moderately enriched pCR rates in the HRDsig(+) group (37.0% vs. 23.8%, odds ratio [OR]=1.87, 95% confidence interval [CI] 0.97-3.84, p=0.08), but not in the HRDsig(-) group (4.5% vs. 5.2%, OR=0.86, 95% CI 0.23-2.55, p=0.767). HRDsig(+) was independently associated with pCR (OR=5.65, 95% CI 2.80-11.89, p&lt;0.001), while platinum Tx and pCR were not associated (OR=0.84, 95% CI 0.23-2.45, p=0.767). A strong treatment interaction between HRDsig status and platinum Tx was not observed (p=0.242, OR=2.24, 95% CI 0.61-9.58). Conclusions: In the neoadjuvant Tx setting, patients with TNBC that were HRDsig(+) were substantially more likely to achieve a pCR. There was a trend towards higher pCR rates among HRDsig(+) patients receiving platinum vs. non-platinum Tx, while this effect was not observed among HRDsig(-) patients. TNBC patients (especially stage II) often experience significant toxicity from chemotherapy regimens. These hypothesis-generating results suggest that HRDsig may help identify patients who achieve additional benefit from platinum agents. These results warrant further evaluation in randomized cohorts to potentially validate this utility.
Postpartum breast cancer: Analysis of factors related to pregnancy and identification of differential prognostic markers.
Authors: Natalia García Cesteros, María López-Herrero López, Geraldina Guevara Madrid, Fernando Mora Martin, Beatriz Teso Martín, Iciar De La Fuente Dominguez, Silvia Guil Luna, Enrique Aranda Aguilar, Juan De La Haba
Journal: Journal of Clinical Oncology (2024)

557 Background: Postpartum breast cancer (PPBC) has an increasing incidence. It is associated with a worse prognosis compared to other breast cancers diagnosed outside of this stage. Objectives: To study clinical and histopathological differences between PPBC (diagnosed within 10 years after delivery) and non-postpartum breast cancer (NPBC, diagnosed more than 10 years after delivery or in nulliparous). Analyze whether reproductive factors such as parity or lactation influence these characteristics. Methods: An observational, analytical and retrospective case-control study is carried out. For the first part, we consider those women with PPBC as case; healthy mothers as control. For the second part, we consider PPBC women as case; NPBC women as control. The data have been analyzed with SPSS v.22. Results: 2698 women under 45 years were recruited. 264 (9.8%) have breast cancer and 2434 (90.2%) are healthy women. The percentage of ex-smokers is higher in PPBC compared to healthy mothers (30.6% vs. 19.7%) (X2=9.632; p=0.022; SS). The proportion of women with previous gynecological pathology is higher in PPBC group than in the group of healthy mothers (48.9% vs. 25.7%) (X2=33.767; p&lt;0.001; SS). The same occurs with previous breast pathology (51.9% vs. 21.7%) (X2=62.75; p&lt;0.001; SS). Women with early PPBC (diagnosed within 5 years after delivery) have higher percentage of previous mastitis compared to the rest of groups that develop tumor beyond 5 years postpartum (20.3% vs. 3.6%) (X2=17.76; p=0.023; SS). The percentage of female pregnancies is more frequent in early PPBC (58.6%) compared to non-postpartum or late PPBC (42.4%) (X2=4.039; p=0.044; SS). The percentage of women who abruptly discontinued breastfeeding is higher in those with PPBC with 27.5% compared to healthy mothers (12.6%) (X2=18.448; p&lt;0.001; SS) (Table). PPBC has higher percentage of stages II (63.9%), the other group of NPBC is mostly diagnosed in stage I (64.9%) (X2=9.808; p=0.002; SS). We found higher elevated expression of Ki67 in early PPBC (90.1%), compared to non-postpartum cancer or late PPBC (77%) (X2=6.252; p=0.012; SS). We observe higher proportion of negative estrogen receptors in early PPBC (36.6%) compared to late PPBC or non-postpartum cancer (13.6%) (X2=9.880; p=0.002; SS). Conclusions: Postpartum breast cancer presents different clinical and histopathological characteristics, highlighting differences in early postpartum period. PPBC has worse prognosis, it constitutes a different entity. Breastfeeding abrupt interruption is associated with development of PPBC. [Table: see text]