bluuebunny/crossref_metadata_2025_split huggingface dataset:
A nomogram to predict pathological complete response of neoadjuvant systemic therapy in HER2-positive breast cancer based on clinicopathologic characteristics and pretreatment systemic inflammation response index: A dual-center study.
Authors: Wu Hong-Yu , Yang Jie-Ru , Hung Chih-Chiang , Yin Chun-Hao , Tzeng Yen-Dun Tony 
Published: June 2022

e12590 Background: Patients with human epidermal growth factor receptor 2 (HER2) positive breast cancer (BC) who achieve a pathologic complete response (pCR) after neoadjuvant systemic therapy (NST) have favorable prognoses. Multiple pretreatment systemic inflammatory markers (SIMs), based on peripheral blood cell counts, have been reported as predictors of pCR in BC patients. The markers include neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, lymphocyte-monocyte ratio, and systemic inflammation response index (SIRI= neutrophil × monocyte / lymphocyte count), etc. However, the most significant SIM remains controversial among studies and the variations among different molecular subtypes remain unknown. Methods: We retrospectively reviewed 233 patients with stage I–III HER2-positive BC who received NST and subsequently underwent surgery in Kaohsiung and Taichung Veterans General Hospital from 2011 to 2021. Data on multiple pretreatment SIMs were collected. The most significant SIM were analyzed for predictive significance with other clinicopathologic factors by using stepwise logistic regression with forward selection. The data was conducted to illustrate a nomogram plot for determining pCR probability. Results: Among the pretreatment SIMs, only SIRI was significantly related to pCR by optimal cut-off value of 1.7 ×109/L. Stepwise logistic analyses indicated that the clinical T and N stage, HER2 immunohistochemistry (IHC) score, PR expression, and targeted therapy regimen were independent predictors of pCR, with an area under the curve (AUC) of 0.74. Sub-analysis was performed after stratifying into T stage subgroups (T1-2 vs. T3-4). Significant predictors In the T1-2 subgroup were clinical N stage, HER2 IHC score, PR, and targeted therapy regimen (AUC=0.722). Significant predictors in the T3-4 subgroup were SIRI and ER (AUC=0.824). The Hosmer–Lemeshow test revealed the predictive ability was a good fit to actual observation. A T-stage-stratified nomogram based on the logistic model was built. Conclusions: In HER2 positive BC patients receiving NST, low pretreatment SIRI is predictive of pCR in T3-4 subgroup. Our nomogram served as an efficient tool to predict pCR and to assist clinical decision support before neoadjuvant treatment.
Impact of capecitabine maintenance on survival outcomes in triple-negative breast cancer patients not attaining pathological complete response following neoadjuvant chemotherapy: Real-world data from a tertiary care center from India.
Authors: Sharma Rakesh Kumar , Gogia Ajay , Sagiraju Hari Krishna Raju , Deo S V Suryanarayana , Sharma Dayanand , Mathur Sandeep 
Published: June 2022

e12593 Background: Capecitabine maintenance has demonstrated a survival benefit in triple-negative breast cancer (TNBC) patients not achieving pathological complete response (pCR) following neo-adjuvant chemotherapy (NACT). However, there is scarcity of data from Indian sub-continent corroborating the benefit of capecitabine maintenance. Methods: This retrospective study comprised of 161 TNBC patients registered at our institute between a period of May 2013 to Dec 2020, who received NACT (sequential anthracycline and taxane) but did not achieve pCR. Capecitabine was added to the institutional protocol since 2017 for maintenance therapy of TNBC patients who didn’t achieve pCR post NACT. Using Kaplan-Meir survival analysis and multivariate cox-proportional hazard models, we analysed differences in the relapse-free survival (RFS) and overall survival (OS) among those who received capecitabine maintenance therapy (n=80) versus those who did not receive it (n=81). Results: Distribution of age, family history, baseline performance score, tumor size, node positivity and clinical stage at time of presentation were comparable between the study groups, except for menopausal status (50% in control vs 33% in capecitabine group). Median(IQR) follow up time was 22.2 (16.2-27.4) months in capecitabine groups vs 19.3 (11.7-35.1) in control group. Twenty-three (28.8%) women in the capecitabine group had a disease-relapse while 45.7% (n=37) had relapsed in control group (p=0.026). Median RFS was 20.4 (17.8-25.9) months in control group while it was not reached in capecitabine group (log rank p=0.007). Adjusted for other baseline clinical characteristics, hazard of disease-relapse was significantly lower in the capecitabine group compared to controls [adjusted Hazard Ratio (aHR), 95% CI: 0.57 (0.34-0.96), p=0.035]. Median OS was not achieved in both the study groups, however, the hazard of death was lower in capecitabine group compared to control [aHR(95%CI): 0.44 (0.20-1.01), p-0.053]. Stratified by menopausal status, effect of capecitabine maintenance on disease relapse and RFS was only significant among the post-menopausal women [aHR (95%CI): 0.24 (0.10-0.59)]. Conclusions: This is the first study from our country, demonstrating a survival benefit with capecitabine maintenance in patients with TNBC not achieving pCR following NACT, particularly in post-menopausal women. It is an important observation as most of our patients present with locally advanced disease where pCR rate is low.
Outcomes of neoadjuvant combination chemotherapy with and without targeted therapy in HER2-positive breast cancer: A real-world experience from tertiary care center in North India.
Authors: Gupta Anshul , Gogia Ajay , Sagiraju Hari Krishna Raju , Deo S.V.S. , Sharma Dayanand , Mathur Sandeep , Gupta Ritu 
Published: June 2022

e12601 Background: Neoadjuvant chemotherapy (NACT) with HER2 blockade is preferred approach for treatment of early and locally advanced HER2 positive breast cancer. However, there is a lack of survival data with respect to pathological complete response (pCR) from India. Methods: We retrospectively evaluated 211 HER2 positive female breast cancer patients registered between years 2014 and 2021, who received three different NACT regimens (i) Anthracycline free TCH (n=116) [docetaxel (75mg/m2), carboplatin (AUC = 6) and trastuzumab (8mg/kg loading followed by 6mg/kg) with G-CSF q 21 days], (ii) EC-TH (n=52) [epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) for 4 cycles followed by 4 cycles of docetaxel (85mg/m2)] and (iii) EC-T (n=43, without trastuzumab due to financial constraints). Primary end point was pCR. Secondary end points were disease free survival (DFS), Overall Survival (OS) and safety profile. Results: Median age was 45 years (24-71), 88 (41.7%) were postmenopausal and 104 (49.3%) were ER/PR positive. Twenty-two (10.4%) patients were stage II, 164 (77.7.%) were stage III and 25 (11.9%) were oligometastatic stage IV. Distribution of age, performance status, tumor size and nodal positivity were comparable across the study groups. Pathological CR in trastuzumab containing groups, was higher compared to non-trastuzumab containing group (35.8% vs 20%, p=0.045) and was similar between, TCH and EC-TH groups. Median follow-up was 32.9 months (5.7-108), 3-year DFS and OS were 54.8% and 92.1% respectively. Pathological CR rates and survival outcomes of the three groups are given in table 1. When stratified by pCR status, in the trastuzumab containing groups, achievement of pCR translated to improved DFS (log rank p=0.01). This survival advantage of pCR was not seen in non-trastuzumab containing group. The outcome of trastuzumab containing both regimens were similar. Grade 3/4 toxicities were recorded in 21.6% of TCH, 26.7% of EC-TH and in 25.2% of EC-T groups. Most common toxicities were anemia (16.3%), thrombocytopenia (14.2%) and vomiting (10.2%). Conclusions: Trastuzumab containing regimens impact pCR rates and in turn the survival outcomes among Indian women with HER2 positive breast cancer. Safety and efficacy of anthracycline free TCH regimen is comparable with EC-TH.[Table: see text]
Comprehensive profiling of cancer associated cells in the blood of breast cancer patients to predict pathological complete response.
Authors: Pore Adity A. , Dhanasekara Chathurika S. , Navaid Hunaiz Bin , Vanapalli Siva A. , Layeequr Rahman Rakhshanda 
Published: June 2022

e12603 Background: Goal of neoadjuvant chemotherapy (NAC) has expanded from increasing the rate of breast conservation to in vivo assessment of response for use of second line therapies that increase survival. Pathological complete response (pCR) is a desirable goal of NAC; however, prediction of pCR for individualized therapeutic decisions remains a vexing problem. Cancer associated cells in the blood provide a promising venue to research response to therapy. Circulating tumor cells (CTCs) are of epithelial origin [CTCs (E+)] that undergo epithelial to mesenchymal transition [CTCs (E+M+)] to become motile and invasive; leading to fully invasive mesenchymal [CTCs (M+)] cells that seed in distant organs, causing metastasis. In addition, cancer associated macrophage-like cells (CAMLs) in the blood of cancer patients are reported to either engulf or aid the transport of cancer cells to distant organs. A comprehensive evaluation of these cancer associated circulating cells through liquid biopsy has a potential to provide a much needed biomarker to predict pCR. Methods: Patients treated with NAC with an intention to cure were enrolled in the study. Blood was collected at 3 time points: pre, mid and post NAC. Microfluidics-based label-free Labyrinth technology was used to isolate CTCs and CAMLs from the blood. Data was collected for patient demographics, biological tumor markers, and treatment response from medical records including pathology reports. Residual Cancer Burden Index (RCBI) and class (pCR vs. residual disease) were analyzed as dependent variables. Independent variables included CTCs, CAMLs and tumor receptor status for univariate and multivariate models to assess the combined effects using R. Results: A total of 57 samples from 19 patients were analyzed. Univariate regression models predicting RCBI or pCR using CTCs and CAML did not show any significant associations. However, in multivariate regression analysis predicting RCBI, an increase in post-NAC CAML and a decrease in post-NAC CTCs were associated with a decrease in RCBI (p=0.005, p=0.035, respectively). In a multivariate logistic regression model predicting pCR, CAML was positively associated with the log-odds of pCR (OR=1.60 [1.01, 2.54]; p=0.047), while CTCs showed a trend in negatively predicting pCR (OR=0.33 [0.10, 1.06]; p=0.063). When controlled for each other, increased CAML and decreased CTCs were associated with increased pCR. While increased M+ was associated with the decreasing log-odds of pCR (OR=0.27 [0.08, 0.99]; p=0.049), neither E+ nor E+M+ was associated with pCR. Conclusions: Increased CAMLs in circulation after treatment combined with lowered CTCs are associated with pCR and lower RCBI. M+ cells could be a factor governing association between CTCs and pCR.
Impact of race on treatment outcomes in triple-negative breast cancer at an academic medical center.
Authors: Patterson Jasmine , Meisel Jane Lowe , Yi Sha , Liu Yuan , Cao Yichun , Li Xiaoxian 
Published: June 2022

e12616 Background: Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, and in all but the smallest tumors, neoadjuvant chemotherapy (NACT) is part of the standard of care. Black women (BW) suffer a poorer prognosis than white women (WW) with TNBC, and whether this is due to differences in treatment, disease biology, or socioeconomic variables is not fully known. This study, conducted at a racially diverse academic medical center, aimed to investigate factors associated with unfavorable outcomes in BW with TNBC. Methods: 131 patients with TNBC received NACT from 2008-2017 at Winship Cancer Institute were included in this retrospective study. Descriptive statistics were applied to delineate the relationship with racial disparity. Clinical outcomes include progression free survival (PFS) and distance metastasis free survival (DMFS) and were analysis using Cox proportional hazard model. Results: Among 131 patients with TNBC treated with NACT, 58.5% were BW and median age was 55. BW and WW had similar disease staging at diagnosis and similar pathologic responses to treatment. Yet, BW were less likely to complete NACT compared with WW (80.8% BW completed NACT vs 98.0% WW, p=0.005). BW were more likely to either not complete NACT or to require dose reduction or dose delay (42.5% BW vs. 23.1% WW, p=0.024). Coexisting hypertension (65.8% BW vs. 35.2% WW), elevated BMI (31.7% BW vs. 27.5% WW), or covered by Medicaid (29.3% BW vs. 13.0% WW) were more common among BW. Medicaid insurance was associated with worse progression-free survival (HR 2.49, p=0.015) and distant metastasis free survival (DMFS, HR 2.73, p=0.018). Dose delays were associated with worse DMFS (HR 3.02, p=0.017). Discussion: In this study, we found that BW were less likely to complete NACT than WW, more likely to suffer dose delays, and more likely to require dose reductions. BW were also more likely to have Medicaid insurance, another factor that correlated with inferior outcomes; perhaps because patients with Medicaid insurance are also more likely to suffer from reduced access to transportation, childcare, and other infrastructure critical to maintaining a schedule for NACT. More research is needed to understand the reasons for the dose delays, dose reductions, and failures to complete NACT so that interventions can be designed to address them. Conclusions: As we move into the era of chemoimmunotherapy for TNBC, where drug combinations and treatment schedules are becoming even more complex, a better understanding of the reasons for dose delays, dose reductions, and treatment discontinuations will be key to maintaining optimal outcomes for TNBC patients, regardless of race.
Real-world data on outcomes using taxane, trastuzumab, and pertuzumab (THP) in patients with early stage HER2+ breast cancer.
Authors: Sharma Harsh , Kreutzfeldt Jordyn , Mehta Tej , Farr Kiah , Brown-Glaberman Ursa , Chalasani Pavani , Nemunaitis Jacklyn , Segar Jennifer Margaret 
Published: June 2022

e12630 Background: In HER2+ early breast cancer, dual HER2 targeted combination of trastuzumab and pertuzumab with chemotherapy achieved higher rates of pathologic complete response (pCR) and improved long term outcomes. However, the optimal chemotherapy backbone is still under investigation. While neoadjuvant taxane in combination with trastuzumab and pertuzumab (THP) has been investigated in NEOSPHERE, patients received anthracycline-based regimen in the adjuvant setting. We report real-world data on long-term patient outcomes after neoadjuvant THP. Methods: An IRB-approved retrospective chart review at 2 academic centers was conducted using EMR to identify women with stage I-III HER2+ breast cancer who exclusively received neoadjuvant THP between 2013-2020. Clinicopathological characteristics and follow up information were extracted from surgical pathology and medical records. Results: 71 patients met criteria (median, 55 years). At presentation, 56 (79%) patients had stage II - III disease and 45 (63%) were lymph node negative. The majority of tumors were ER+ (43 patients, 61%) and received paclitaxel (46 patients, 65%) as their taxane backbone. pCR was achieved in 40 (56%) patients (Table); 38 (95%) continued with adjuvant HER2 therapy alone; 1 received adjuvant endocrine therapy only and 1 received no further treatment. Of the 31 (44%) patients without pCR, 9 received additional adjuvant chemotherapy in addition to HER2 directed therapy while 18 continued with HER2 therapy alone. During the follow-up period (median 34.7 mo, range 6.8-98.9 mo), 3 patients with lymph node positive disease on presentation had disease relapse. Two of the patients with pCR had local recurrence and one without pCR had distant metastasis (brain, lung). The 2 patients with local recurrence were successfully treated with salvage therapy and remain in remission. The patient with metastatic disease remains alive and on treatment. Conclusions: We showed that a real world HER2+ patient population treated with neoadjuvant THP achieved pCR rates consistent with what has been previously reported. In addition, with a median follow up of ̃ 3 years, only 3 patients had relapse supporting the utility of THP as potential de-escalation treatment in the neoadjuvant setting. Ongoing prospective trials, like NCT03716180, will further confirm the efficacy of this regimen in a prospective setting.[Table: see text]
Importance of accurate clinical staging in patients with early stage HER2+ and triple negative breast cancer.
Authors: Sidda Adarsh , Biglow Layana Roslyn , Manu Gurusidda , Abdallah Mahmoud , Tirona Maria R.B. Tria 
Published: June 2022

e12631 Background: Comprehensive radiological evaluation in early-stage breast cancer is essential for accurate staging and subsequent therapeutic decisions. This is especially important in early-stage human epidermal receptor -2 (HER2) positive and triple negative breast cancer (TNBC). For these tumors, current guidelines suggest a neoadjuvant approach for ≥cT2 disease. Standard diagnostic modalities have oftentimes failed to confirm the correct size of these tumors. Misrepresentation of their true size may lead to patients being treated with upfront surgery and potentially missing the added benefits of residual treatment if they were later found to have >T2 disease. Methods: We conducted a retrospective analysis via electronic medical record review of a large institutional database from 2008 to 2020. We reviewed all patients with a diagnosis of early-stage breast cancer (Stage I - III) with triple negative or HER2 positive tumors. Patients who received neoadjuvant chemotherapy were excluded. Data on demographics, comorbidities, receptor status, clinical staging, pathological staging, and mortality were collected. Results: Electronic charts from 448 patients were reviewed. 153 patients had ≤cT1 disease. 33 (21.6%) of the 153 patients were upstaged from cT1 to ≥pT2 tumors. Combined imaging modality with mammogram + ultrasound (US) yielded a statistically significant accuracy in clinical staging compared to US alone (82.6 vs. 44.4%; p = 0.02). Comparisons between other imaging methods were not statistically significant (mammogram + US vs. mammogram only, 74.1 vs. 82.6%, p = 0.41 and mammogram only vs. US only, 74.1 vs. 44.4%, p = 0.13). Magnetic Resonance Imaging (MRI) was only utilized on 2 patients with 50% accuracy. Conclusions: Significant discordance (> 20%) exists between radiological staging and pathological staging of T1 TNBC and HER2 positive breast cancers at our institution. This data has considerable therapeutic implications as landmark studies such as the CREATE-X and KATHERINE trials have provided better survival data with the use of drugs such as capecitabine and trastuzumab emtansine (T-DM1), respectively, in patients with residual disease who have undergone neoadjuvant chemotherapy followed by surgery. Combined imaging with mammography and US yielded the most accurate staging. MRI was utilized on only two patients. MRI has shown to be helpful in evaluation of patients for preoperative systemic therapy, defining the extent of disease, assessing response to treatment and the potential for breast conserving surgery. Several studies have also demonstrated the accuracy of MRI for staging breast cancer. Given the significant discordance seen at our institution, one possible solution may be to employ MRI for staging on patients with inherently aggressive early-stage tumors such as TNBC and HER2+ breast cancers. Further prospective studies are required to validate our findings.
Improved sensitivity in identification of first recurrences of metastatic breast cancer with a combination of cell and cell-free liquid biopsy analysis.
Authors: Di Caro Giuseppe , Bourdon David , Byun Jiyun , Singer Tatjana , Anderson Amanda , Blankfard Martin , Tubbs Alisa , Wenstrup Rick 
Published: June 2022

e13003 Background: Liquid biopsy analysis detecting circulating tumor cells (CTC) or circulating tumor DNA (ctDNA) is a non-invasive approach that may provide clinically actionable information for patients’ (pts) treatment decisions when conventional biopsy is otherwise inaccessible or infeasible. Here we report a liquid biopsy method including CTC characterization & ctDNA alterations in pts symptomatic of first metastatic recurrence with a history of primary breast cancer (BC). Methods: Blood samples from 34 symptomatic BC pts were collected for cell & cell-free DNA analysis before undergoing contemporaneous tissue biopsy & initiating treatment for metastatic BC (MBC). Blood was also collected from 25 blood donors (HD) with no known cancer history. After plasma isolation, nucleated cells were plated, & slides were bio-banked. Immunofluorescent staining & subsequent imaging were performed on replicate slides. CTCs were identified using Epic Sciences digital imaging & machine learning algorithms trained to identify breast cancer cells. Single-cell (sc) isolation for genomic quantification of large-scale transitions (scLST) was used to further characterize individual CTCs. cfDNA from bio-banked plasma was analyzed to detect Class IA alterations in ctDNA. Results: Within this cohort of 34 patients, CTCs & ctDNA alterations were detected in 80% & 58%, respectively while no CTCs & ctDNA were detected in the HD cohort suggesting high specificity (100% & 100%). In this study, 26 pts were confirmed MBC (M1-BC) by tissue biopsy, 3 pts were non-MBC by tissue biopsy but still diagnosed as metastatic (Mx-BC), & 5 pts were confirmed non-MBC (M0-BC). To benchmark the cellular (CTCs & scLST+CTCs) & genomic (ctDNA) individual platforms, we designed thresholds of CTCs > 4, scLST+CTC+, & ctDNA+ that optimally identified M1-BC pts with high specificity (100%, 100%, & 100%) but low sensitivity (46%, 46%, & 50%). CTCs > 4 & scLST+CTC+ cutoffs had low concordance with the presence of ctDNA alterations, suggesting these platforms provide independent & complementary value when identifying MBC. To test this hypothesis, we designed combination models [CTC > 4][ctDNA+] & [scLST+CTC+][ctDNA+] that significantly improved sensitivity (75% & 67%) over individual platforms while maintaining high specificity (100% & 100%) when identifying the first recurrence of metastasis in BC pts. Conclusions: To our knowledge, this is the first report showing the additive & complementary value of models combining cellular & genomic liquid biopsy platforms for the detection of the first MBC recurrence. Our data suggest the clinical utility of combined CTC & ctDNA platforms for the identification of MBC when tissue biopsy is inaccessible or infeasible.