bluuebunny/crossref_metadata_2025 huggingface dataset:
Are we using the right cut-offs to obtain maximum information from Ki-67 in patients with early breast cancer?
Authors: Trifanescu Oana Gabriela , Bilteanu Liviu , Ilie Silvia , Bran Diana Maria , Safta Inga , Gales Laurentia Minea , Anghel Rodica Maricela
Published: June 2023

e12567

Background: Ki-67 is one of the most critical prognostic proliferation markers in breast cancer, used on a large scale by oncologists to select treatment options. This study aimed to validate Ki-67 as a prognostic marker and establish the optimal Ki67 cut-offs for stratifying patient prognosis and treatment decisions. Methods: Medical files of 582 consecutive patients with early breast cancer (stage IB-IIIA) who underwent surgery as a first treatment in our institution between 2005-2019 were retrospectively reviewed. Values of Ki-67 were divided into 5 categories: 0-9%, 10-19%, 20-29%, 30-39%, and more than 40%. Results: Kolmogorov-Smirnov and Shapiro-Wilk tests showed that the patient’s age (yrs) at diagnostic, Ki-67 (in %), tumor size (in mm), estrogen and progesterone receptors abundance (%), exhibit normal distributions (p < 0.05). Median age at diagnosis was 54.8 (± 11.5) years and mean Ki-67 of 25.5 ± 16.5 and a median value of 20. Stage distribution was: stage IB 5.5%, IC 12%, IIA 46.6%, IIB 20.4%, IIIA 15.5%. The mean tumor dimension at diagnosis was 21.3 mm. After a median follow-up of 48 months (6-118), estimated disease-free survival rates (DFS) for all patients at 3 and 5 years were 92% and 79%. Disease-free survival rates at 5 years was 96% for patients with Ki-67 0-9%, 90% for patients with Ki-67 10-19%, 80% for patients with Ki-67 20-29%, 75% for patients with Ki-67 30-39%, and 72% for patients with Ki-67 more than 40%. The difference between the median DFS and each ki67 category was statistically significant (p < 0.0001). Using the fit of mixture method, we identify a new cut-off of 29% that negatively predicts DSF for patients (HR = 4.51 95% CI = 1.69-12.04, p = 0.001). Pearson correlation coefficients (p < 0.05) for Ki-67 and DFS, age, ER%, PR%, p53, and tumor size were -0.110, -0.096, -0.139, -0.136, 0.301, and 0.175, respectively. Moreover, DFS was also negatively correlated (p < 0.01) with the patient’s age (-0.106) and tumor size (-0.180). Though the correlation coefficients were small, they oriented the creation of linear models of DFS as a dependent variable and Ki-67, tumor size, and age. DFS has a statistically significant dependence only on the first two variables (standardized coefficients -0.103, p = 0.045 and -0.161, p = 0.02). Conclusions: Ki-67 is a strong prognostic factor in early breast cancer patients. New Ki-67 cut-off levels that may be used in clinical practice were identified. In addition, multivariate analysis showed a significant statistical influence of other factors, such as Ki67 and tumor size. Such correlations can be the basis of a scoring system for progression risk.
Clinicopathological characteristics and outcome of very young breast cancer patients at a referral center in Iran.
Authors: Malekzadeh Moghani Mona , Hashemi Atieh Sadat , Bazgir Narges
Published: June 2023

e12568

Background: Although breast cancer (BC) is the most common type of cancer in women worldwide, in women younger than 35 years old is uncommon and only accounts for 2% of breast cancer diagnosed in western countries. However, there is insufficient data on breast cancer in women younger than 35 years old in Iran. The aim of this study was to assess clinicopathological parameters in these very young breast cancer patients. Methods: In this retrospective cohort study, we have collected the demographic, clinical and histopathological data of women younger than 35 years diagnosed with BC who presented to our tertiary center from 2011 to 2017. Patients were followed at least for four years and the diseases-free survival (DFS) and overall survival (OS) were assessed. Chi-square and multivariate regression tests were conducted to assess the association of mentioned variables. A P-value less than 0.05 was considered to be statistically significant. Results: A total of 334 women with Breast Cancer younger than 35 years old were included in this study, of which 219 patients were between 31 to 35. The most common histopathologic type was hormone receptor positive, HER2 negative 41.6 %. HER2 positive (regardless of hormone receptor status) and triple negative were 30.1% and 24.6% of cases respectively. Grade1 was reported in 5% of cases, grade 2 and 3 were 50.9 % and 43.6% respectively. 16.9% of patients were presented in stage I, 44.4% stage II, 30.5% stage III and 8.2% had de novo metastatic disease. Of 68 patients who received neoadjuvant chemotherapy, 29.4% had complete pathological response. Sixty five percent of 199 patients with hormone positive had received Luteinizing hormone-releasing hormone (LHRH) agonist, this type of treatment significantly improved 4-year OS regardless of HER2 expression. Mean follow up was 71.5±26.6 months, 4-year DFS and OS were 66% and 80% respectively. Four-year overall survival was analyzed by stage, it was 100% for stage I, 89% stage II, 79% stage III, and 11% stage IV. The four-year OS corresponding to the subtypes was as follows; HR+/HER2- (89.5%), HR+/HER2+ (76.9%), HR-/HER2+ (73.3%) and TNBC (75.4%). Conclusions: Breast cancer occurring in very young women constituted 9.5% of all breast cancer cases treated at Shohada Hospital, Iran, and this high rate shows a significant correlation with unpublished data by Health ministry in 2016-2017. This high percentage is an alarm not only in breast clinics but also in early detection of breast cancer. In according to other published data, clinicopathological subtypes in our center was similar to other papers. The associations of subtypes with stage and grade, were significant.
Incidence of hypomagnesemia in patients with HER2+ breast cancer treated with pertuzumab.
Authors: Shah Nirja , Daily Karen Colleen
Published: June 2023

e12569

Background: Breast cancer is the most common cancer diagnosed in women. HER2 gene amplification/protein overexpression is seen in about 20% of breast cancer cases. Pertuzumab (P), an EGFR inhibitor, is a monoclonal antibody administered with Trastuzumab in the treatment of HER2-positive breast cancer. Breast oncologists across multiple institutions have noted hypomagnesemia in patients receiving P-containing regimens. Retrospective data from Memorial Sloan Kettering Cancer Center and University of Florida Health have reported the incidence of hypomagnesemia in patients treated with P neoadjuvantly (8/90 and 7/25, respectively). Cetuximab and Panitumumab, also EGFR inhibitors, are well known to cause hypomagnesemia. Hypomagnesemia can be clinically associated with convulsions, atrial tachycardias, hypocalcemia and hypokalemia. This prospective study details the incidence, severity, and timeline of hypomagnesemia in HER2-positive breast cancer patients treated with P. Methods: 27 eligible patients were identified at two institutions through medical oncology clinic visits and weekly tumor board screenings. Inclusion criteria was HER2+ breast cancer patients initiating treatment with P. Patients receiving platinum agents were excluded (8/27). Following informed consent, magnesium levels were obtained along with standard of care comprehensive metabolic panels at the first four P infusions (19/27). Results: A one-sample binomial test was used to compare the proportion of hypomagnesemia at 3 months among subjects who receive P with 2% (historical control). Results demonstrated that only one patient developed a magnesium level below normal range, resulting in no significant difference with historical control (P = 0.291) This patient’s magnesium level was low at baseline and did not significantly improve or worsen throughout treatment with P. Conclusions: There was no significant incidence of hypomagnesemia noted in HER2+ breast cancer patients treated with P. This emphasizes the safety of P in patient populations prone to developing hypomagnesemia such as those receiving concurrent Carboplatin. Our results do not indicate clinical monitoring of hypomagnesemia is necessary for patients receiving P. [Table: see text]
Oncologic outcomes for different axillary staging techniques in nodal positive breast cancer undergoing neoadjuvant systematic treatment: A cancer registry study.
Authors: Pfob André , Kokh Daria , Surovtsova Irina , Riedel Fabian , Heil Joerg , Morakis Philipp ,   KRBW (Krebsregister Baden-Württemberg)
Published: June 2023

e12571

Background: The optimal axillary staging technique for patients with nodal positive breast cancer undergoing neoadjuvant systemic treatment (NAST) is unclear. Less invasive, targeted approaches like targeted axillary dissection (TAD) or sentinel-lymph node biopsy (SLNB) recently showed false-negative rates < 10% compared to axillary lymph node dissection (ALND). Oncologic outcomes, however, are unknown. Methods: We identified nodal positive breast cancer patients undergoing NAST from 2016 to 2021 with at least 1-year follow-up and available information regarding axillary staging from the state cancer registry of Baden-Wuerttemberg, Germany. Invasive disease-free survival (iDFS) was assessed using Kaplan-Meier statistics and multivariate cox regression models (adjusted for age, pN stage, pT stage, and tumor biologic subtype). Results: A total of 2403 patients with a median follow-up of 23.2-months after surgery were identified: 1963 underwent ALND, 407 underwent SLNB (in 230 cases, three or more sentinel nodes (SLNs) were removed and in 177 cases, 1-2 SLNs were removed), and 33 underwent TAD. The proportion of patients with pN+ stage within these four groups was 54%, 31%, 26%, and 35%, respectively ( P < 0.001). Significant differences in iDFS between the ALND, SLNB, and TAD groups were observed (log rank P = 0.046): iDFS 2 years after surgery was 74.5% (ALND), 80.2% (SLNB ≥3 removed SLNs), 85.6% (SLNB < 3 removed SLNs), and 88.4% (TAD), respectively. iDFS after 4 years was 61.5% (ALND), 69.1% (SLNB ≥3 removed SLNs), and 74.6% (SLNB < 3 removed SLNs), respectively. Multivariate cox regression analysis showed no significant influence of different axillary staging techniques on iDFS: HR 0.91 (95% CI 0.55 to 1.52) for SLNB with ≥3 removed SLNs, HR 0.99 (95% CI 0.59 to 1.67) for SLNB with < 3 removed SLNs (reference = ALND). Conclusions: This data suggests that ALND provides no benefit in terms of iDFS compared to targeted approaches like TAD or SLNB for patients with nodal positive breast cancer undergoing NAST. Future studies with longer-term follow-up are welcomed to fully inform this discussion.
Impact of distance between tumor and nipple on survival outcomes in breast cancer.
Authors: Cheun Jong-Ho , Kang Eunhye , Chun Jung Whan , Kim Hong-Kyu , Lee Han-Byoel , Moon Hyeong-Gon , Han Wonshik , Hwang Ki-Tae
Published: June 2023

e12579

Background: Mastectomy is usually recommended surgical procedure for centrally located tumors regarding the increased risk of nipple invasion. Despite no difference in survival outcomes based on tumor locations, central tumor may have a higher chance of main lactiferous duct invasion, leading to tumor cell can migration to periphery of the breast. In this study, we investigated the relationship between locoregional recurrence (LRR) and the tumor-to-nipple distance (TND). Methods: We retrospectively analyzed the data of patients who underwent breast cancer surgery between 2004 and 2018 at two institutions. Patients who underwent neoadjuvant chemotherapy were excluded. TND was measured using preoperative MRI records. Results: A total of 9,014 patients were included, and median TND was 3.4 (0.0-15.0)cm. A restricted cubic spline curve showed that the hazard risk of LRR increased with shorter TND for all patients. While the risk of LRR appeared to apparently increase in the breast-conserving surgery (BCS) group, the mastectomy group showed the constant pattern. Thus, we conducted survival analysis for 5,455 patients who underwent BCS. We set the TND cutoff at 2.5 cm, which showed the lowest p-value for LRR rate. Compared to those with TND > 2.5cm, patients with TND≤2.5cm had significantly lower rates of LRR (HR,1.83; 95%CI,[1.37-2.46], p < 0.001) and distant metastasis (DM) (HR,1.53; 95%CI,[1.16-2.02], p = 0.002). However, overall survival was not different between the two groups (p = 0.405). Cox-regression analysis showed that TND still had a significant impact on LRR (HR,1.52; 95%CI,[1.11-2.09], p = 0.010) but not on DM. Importantly, TND still remained significant factor affecting LRR when analyzed as continuous variable (HR,1.04; 95%CI,[1.02-1.06], p < 0.001). The prognostic impact of shorter TND was more evident in patients with high mammographic density. Conclusions: BCS can be considered a safe option for central tumors, but mastectomy could be a better choice for patients who are concerned about recurrence or unwilling to undergo additional surgeries.
A meta-analysis of cardiac toxicity of concurrent epirubicin and trastuzumab in early breast cancer.
Authors: Yang Minghan , Huang Chiun-Sheng , Chang Dwan-Ying , Chen I-Chun , Lin Ching-Hung , Lu Yen-Shen
Published: June 2023

e12583

Background: The concurrent use of doxorubicin and trastuzumab has been limited due to the increased risk of cardiac toxicity. Epirubicin is a less cardiotoxic alternative to doxorubicin, and the change in ejection fraction occurs until its cumulative dose doubles that with doxorubicin. This study aims to evaluate the cardiotoxicity and pathological complete response (pCR) rate associated with concurrent usage of epirubicin and trastuzumab in patients with HER2 positive early breast cancers (EBC). Methods: A literature search was conducted on NCBI/PubMed, and Cochrane database for phase II or III randomized controlled trials of concurrent use of epirubicin and trastuzumab in HER2 positive EBC between January 1, 2000 and February 28, 2021.The definition of adverse cardiac events varied among these trials, including changes in left ventricular systolic function and clinical heart failure. To compare the risk of cardiotoxicity and the odds of pCR rate between concurrent and non-concurrent regimens, a meta-regression analysis utilizing fixed-effects and mixed-effects linear models was conducted to investigate the relationship between various covariates. Results: Seven trials containing concurrent use of epirubicin and trastuzumab involving 1797 patients were analyzed. All of them are neoadjuvant studies. The median cumulative dose of epirubicin used was 300mg/m2 and there were a total of 96 reported cardiac adverse events. The concurrent use of epirubicin and trastuzumab did not result in a statistically significant increase in cardiotoxicity compared to non-concurrent regimens (risk ratio = 1.18, 95% CI: 0.68-2.05). Meanwhile, there was a significant increase in pCR rate with the concurrent regimens (odds ratio = 1.48, 95% CI: 1.04-2.12). Mixed-effects meta-regression analysis showed that in trials with higher proportion of hormone receptor-positive EBC patients, the risk ratio of cardiotoxicity significantly increased with concurrent regimens and pathological complete response rate became less significant. Conclusions: The concurrent use of a limited dose of epirubicin and trastuzumab demonstrated a positive impact on pCR rate without a significant increase in cardiotoxicity. Further research is necessary to fully comprehend the long-term safety profile in individuals with metastatic breast cancer. [Table: see text]
Association of circulating tumor DNA with survival in neoadjuvant-treated triple negative breast cancer independent of pathological complete response.
Authors: Li Yan , Chen Xiaobin , Lin Yuxiang , Fu Fangmeng , Wang Chuan
Published: June 2023

e12588

Background: Many patients with triple negative breast cancer (TNBC) still succumb to their disease after systematic treatment. It is crucial to identify those at high risk. Circulating tumor DNA (ctDNA) has recently become a promising marker to monitor tumor burden. Our study aimed to evaluate the clinical value of the presence and dynamic change of ctDNA to predict the tumor response and prognosis in TNBC patients treated with neoadjuvant chemotherapy (NAC). Methods: Cell-free DNA (cfDNA) was isolated from pre-NAC plasma samples and then analyzed by duplex sequencing. A Chi-square test or Fisher exact test were used for categorical variables. Kaplan‐Meier analysis with a Log‐rank test and the Cox proportional hazard regression model were used for the univariate and multivariable survival analysis. Survival prediction was assessed using a time-dependent receiver operating characteristic (ROC) curve and area under the ROC curve (AUC). Results: A total of 82 TNBC patients receiving NAC were enrolled. Baseline ctDNA detection indicated significantly worse survival. TP53 and genes involved in PI3K-Akt signaling pathway mutations were significantly associated with survival independent of the pathological complete response (pCR). A TP53 detection combined clinical model is highly predictive, with a time-dependent ROC of 0.936 for 3-year overall survival (OS), compared to the model including clinical variables only (AUC of the clinical predictor: 0.751, P= 0.028). Conclusions: Baseline ctDNA detection, TP53 mutations, and genes involved in PI3K-Akt signaling pathway mutation are all independent prognostic factors in TNBC patients receiving NAC. A TP53 detection combining model is highly predictive.
Real-world, single-center experience on the outcomes of neoadjuvant chemotherapy and trastuzumab alone or in combination with pertuzumab in human epidermal growth factor receptor-2 breast cancer patients.
Authors: Vaid Ashok Kumar , Sharma Devender , Wadhwa Jyoti , Agarwal Rajeev Kumar , Kaur Kanchan , Goyal Shina , Gautam Dheeraj , Arora Jyoti , Gupta Sabhyata , Goel Ruchika , Sen Ashok
Published: June 2023

e12589

Background: Neoadjuvant chemotherapy (NACT) is the standard of care for early-stage breast cancer (BC). Human epidermal growth factor receptor 2 (HER2) positive disease constitutes a large proportion of BC patients, and HER2 overexpression is associated with poor prognosis. The introduction of HER2+ targeted therapies, such as trastuzumab and pertuzumab, has resulted in improved outcomes in HER2+ BC. NACT in combination with HER2 targeted therapies aims at achieving pathological complete response (pCR) and an improved survival rates. Methods: We performed a retrospective review of HER2+ BC patients who were treated at Medanta – The Medicity Hospital, Gurugram, Haryana, India, between 2011 and 2021. A total of 108 HER2+ BC patients who received NACT with platinum, anthracycline or taxane-based regimens, along with trastuzumab alone or in combination with pertuzumab, were included. Results: Of 108 enrolled patients, 66 and 42 patients received neoadjuvant single-blockade (trastuzumab) and dual-blockade (trastuzumab and pertuzumab) anti-HER2 therapy, respectively. The majority of patients were aged < 60 years. The patient populations were comparable in terms of clinical stage, hormone receptor status, histopathology category [Invasive ductal carcinoma (IDC) being most common] and Ki67 status for both groups. All patients had IHC3+/FISH+ HER2 expression. No significant (p = 0.896) difference was observed for breast conserving surgery between the groups. A higher pCR rate after surgery was reported in the dual-blockade versus single-blockade group (50% vs. 39.2%; p = 0.271). The median follow-up duration was 21.9 and 15.2 months in the single-blockade and dual-blockade groups, respectively. For dual- vs. single- blockade groups, the 1-year OS rates were 100% each, and 3-year OS rates were 100% vs. 98.48%. For dual- vs. single- blockade groups, the 1-year DFS rates were 100% vs. 95.45%, and 3-year DFS rates were 92.85% vs. 80.3% respectively. Conclusions: Neoadjuvant chemotherapy with dual HER2-blockade had higher pCR and survival rates compared with the single HER2-blockade strategy in HER2 positive breast cancer. [Table: see text]
Factors associated with response to neoadjuvant chemotherapy and immune checkpoint inhibition in triple-negative breast cancer.
Authors: LeVee Alexis , Wong Megan , Flores Sarah , Ruel Nora H. , Lavasani Sayeh Moazami , Patel Niki , Sedrak Mina S. , Stewart Daphne B. , Waisman James Ross , Yuan Yuan , Mortimer Joanne E.
Published: June 2023

e12593

Background: Immune checkpoint inhibition with pembrolizumab plus neoadjuvant chemotherapy is now the standard-of-care in patients with high-risk triple-negative breast cancer (TNBC) based on the KEYNOTE-522 trial. The trial demonstrated that the addition of pembrolizumab improves pCR, but it is currently unclear which patients benefit most from the addition of immunotherapy (IO). We sought to identify which demographic and clinical characteristics were associated with response to neoadjuvant pembrolizumab plus chemotherapy. Methods: We performed a single institution, retrospective study of early-stage TNBC patients treated with neoadjuvant chemotherapy and pembrolizumab between March 1st, 2020 and December 1st, 2022. We excluded patients who had not undergone definitive surgery. We collected demographic information, clinical and pathologic characteristics, and treatment data. Pathologic complete response (pCR) was defined by ypT0/Tis and ypN0. Multivariate analysis was performed using logistic regression to identify factors associated with pCR. This study was approved by the City of Hope Institutional Review Board. Results: 67 patients were analyzed with a median age of 56 years and median BMI of 29. Self-reported racial groups included 25 Hispanic patients (37%), 23 non-Hispanic White (34%), 9 Asian (13%), 6 Black (9%), and 4 other/unknown (6%). 6 (9%) patients were BRCA1+ and 1 (1.5%) patient was BRCA2+. The majority of patients had invasive ductal carcinomas (91%), were clinical T2 stage (65.7%), and node negative (52.2%). The median number of cycles of neoadjuvant IO was 7 (IQR 4-8) and median months from start of IO to surgery was 6 (IQR 4.6-6.7). 42 (62.7%) patients had a pCR. Multivariate results showed that patients under 50 years at time of diagnosis (vs. age > 50 years), those with grade 3 (vs. 2), and those receiving 7 or more cycles of pembrolizumab (vs. < 7) had improved rates of pCR (ORs 5.7, 8.1, and 3.4, respectively, p < 0.05). BMI, race, BRCA1/2 status, histopathology, clinical T and N stage, and timing of start and end of IO to surgery were not significantly associated with pCR. Conclusions: Younger TNBC patients with high tumor grade were more likely to respond to treatment with neoadjuvant pembrolizumab and chemotherapy. More cycles of treatment with pembrolizumab was also associated with response. Further research to identify which patients with TNBC benefit from the addition of pembrolizumab to chemotherapy is necessary to determine whether its additional toxicity and cost are warranted.
Phase II neoadjuvant trial of albumin-bound paclitaxel, trastuzumab and pertuzumab followed by anthracycline based regimens in patients with operable HER2 positive breast cancer (OMC-BC05).
Authors: Iwamoto Mitsuhiko , Ikari Ayana , Tominaga Tomo , Maezawa Saki , Sakane Junna , Oku Hiroyo , Yoshidome Katsuhide , Morimoto Takashi , Fujioka Hiroya , Hagihara Seita , Nitta Toshikatsu , Matsutani Ayumi , Kimura Kosei
Published: June 2023

e12594

Background: Anthracycline and Taxane have been widely used and studied in neoadjuvant setting for treatment of locally advanced breast cancer. Various regimens have explored the addition of newer agents to determine safety and efficacy, and pathological complete response(pCR) has been demonstrated to be associated with favorable overall survival in primary breast cancer. Pertuzumab increases the rate of pathological complete response in the preoperative context and increases overall survival among patients with metastatic disease when it is added to Trastuzumab and chemotherapy for the treatment of human epidermal growth factor receptor 2 (Her2)-positive breast cancer. In addition, APHINITY trial showed that Pertuzumab significantly improved the rates of invasive-disease-free survival among patients with HER2-positive, operable breast cancer when it was added to Tastuzumab and chemotherapy. We conducted a clinical phase II neoadjuvant trial of nab-Paclitaxel, Trastuzumab and Pertuzumab followed by Anthracycline Based Regimens in Patients with Operable Her2 Positive Breast Cancer. Methods: The study is designed to evaluate nab-paclitaxel, Trastuzumab and Pertuzumab followed by EC or AC or FEC as neoadjuvant therapy in patients with Her2 positive operable breast cancer. Patients are treated with neoadjuvant nab-paclitaxel(260 mg/m2 ), Trastuzumab and Pertuzumab followed by EC(Epirubicin 90 mg/m2 , Cyclophosphamide 600 mg/m2) or AC(Doxorubicin 60 mg/m2 , Cyclophosphamide 600 mg/m2) or FEC(Fluorouracil 500mg/m2, Epirubicin 100 mg/m2 , Cyclophosphamide 500 mg/m2 ) q21d x 4. Patients undergo surgery 4-6 weeks later from completing chemotherapy. The primary endpoint, pCR is defined as no evidence of invasive tumors in the final surgical sample both in the breast and axillary lymph nodes. Secondary endpoints include overall response rate, disease-free survival, rate of breast conserving surgery, histological response rate, rate of sensory neuropathy ant the safety of the treatment. Results: In 30 evaluable patients, the pCR rate was 50%; 6/19 (31.6%) in ER-positive and 9/11 (81.8%) in ER-negative, 1/7 (14.3%) in IHC 2+, FISH positive and 14/23 (60.9%) in IHC 3+ . Of the study treatments, the most frequent reason for delay or dose reduction was hematologic toxicity; no patient required a dose reduction for nab-PTX because of peripheral neuropathy. Conclusions: Neoadjuvant treatment using albumin-bound Paclitaxel, Trastuzumab and Pertuzumab followed by Anthracycline based regimens appears to be effective especially in pure HER2 type or IHC 3+ cases.
Informative tools to optimize neoadjuvant therapy in ER positive, HER2 negative breast cancers.
Authors: Luzhna Lidiya , Chia Stephen , Pauls Mehrnoosh , LeVasseur Nathalie
Published: June 2023

e12595

Background: Neoadjuvant therapy (NAT) in HR+/HER2- tumors is often disputable. While the role of Oncotype DX has been well established in adjuvant settings, its clinical utility and potential implementation for prediction of NAT benefit requires further study. This ongoing study aims to report the feasibility of Oncotype DX testing on core biopsy specimens prior to NAT in patients with operable HR+/HER2- breast cancer. The effect of the recurrence score (RS) on systemic treatment recommendations and its correlation to dynamic markers of proliferation and NAT response will be evaluated. Methods: Participants with clinical T2-T4 and/or node positive HR+/HER2- breast cancer had Oncotype DX testing done prior to NAT. Clinico-pathological information, treatment regimens, clinical, radiologic, and pathological responses were recorded. Results: Of the 48 patients with HR+/HER2- breast cancer referred to BC Cancer Vancouver for consideration of NAT between September 2021 and January 2023, 26 were eligible and enrolled in the study. The success rate of the Oncotype DX on core biopsy samples was 96%. The mean turnaround time from patient consent to RS report was 19 calendar days. Approximately 32% of tumors had a RS equal or higher than 26 while 4% had a score less than 10. Nearly 25% of neoadjuvant treatment recommendations were changed based on the RS. Overall, 33% of patients received neoadjuvant chemotherapy, 54% received neoadjuvant endocrine treatment, and 12.5% proceeded with upfront surgery. Conclusions: The success rate of Oncotype DX testing on core biopsy samples was excellent. There were multiple factors that influenced trial enrollment, highlighting the low uptake and equipoise of NAT use in HR+/HER2- tumors. The Oncotype DX testing resulted in a change in systemic treatment plan in 25% of patients. Analyses are ongoing to correlate the recurrence score to NAT response, dynamic Ki-67 changes and breast MRI changes. Clinical trial information: NCT03790813 .
The impact of exercise training on the pathologic response and tumor immune microenvironment in breast cancer after neoadjuvant chemotherapy: An exploratory study.
Authors: Guedes Helena , João David , Antunes Pedro , Silva Sandra , Leão Inês , Esteves Dulce , Helguero Luisa , Costa Telma , Viamonte Sofia , Alves Alberto , Caldas Margarida , Joaquim Ana
Published: June 2023

e12596

Background: In early breast cancer (BC), pathological complete response (pCR) is an efficacy endpoint of neoadjuvant chemotherapy (ChT) and percentage of tumor-infiltrating lymphocytes (TILs) is a prognostic biomarker. Although exercise training is an evidence-based supportive care across the BC journey, one open question is its impact on the antitumor effect of neoadjuvant ChT. The authors aim to investigate the effects of a supervised exercise training program (STEP) in pCR and TILs in BC women undergoing neoadjuvant ChT. Methods: MAMA_MOVE_Gaia on Treatment (ISRCTN, ISRCTN32617901) is randomized controlled trial in which women with early BC undergoing anthracycline containing ChT were randomized in a 1:1 ratio to a SETP or to usual care, close to recruitment in January 2022. For this exploratory analysis, we retrospectively identified patients who underwent neoadjuvant ChT, and compare pCR and TILs between the two arms. Results: Sixty-four participants were included, aged from 26 to 72 years old (mean = 50.3, SD = 10.1) majority with stage II and III (n = 58, 90,6%) and HER2+ (n = 23, 35.9%) or triple negative (n = 19, 29.7%) disease. The pCR in STEP arm had a prevalence of 56.7% and in the usual care arm of 55.9%(p = 0.950). In the STEP arm median TILs were, for the biopsy and tumor site, of 5.0 (range 0.0-80.0) and 5.0 (range 5.0-30.0). In the usual care arm, median TILs were, for the biopsy and tumor site, of 5.0 (range 0.0-90.0) and 0.0 (range 0.0-30.0). There was no difference between groups for TILs of the biopsy (p = 0.907). Higher TILs of the tumor site was marginally associated with the STEP arm (p = 0.082). Conclusions: Despite the results obtained, it is believed that a larger sample may lead to different results. However, these data could also support future research in this field, bringing new insights for cancer survivors continuum of care.
National trends in neoadjuvant chemotherapy utilization for cT1-2 N0 triple negative breast cancer: Did the CREATE-X trial impact treatment patterns?
Authors: Rogers Christine , Lloren Jan Irene , Johnson Morgan K. , Cobb Adrienne , Chaudhary Lubna Naaz , Huang Chiang-Ching , Teshome Mediget , Singh Puneet , Kong Amanda L. , Cortina Chandler Scott
Published: June 2023

e12599

Background: Neoadjuvant chemotherapy (NAC) for operable breast cancer allows for in-vivo assessment of chemotherapy response with survival and therapeutic implications. In 2017, the Capecitabine for Residual Cancer as Adjuvant Therapy (CREATE-X) trial demonstrated significant improvement in survival with the addition of adjuvant capecitabine in patients with triple negative breast cancer (TNBC) and residual disease after NAC. These results provided the rationale for NAC even in early stage TNBC. The aim of this study was to assess U.S. national rates of NAC utilization in early-stage node-negative TNBC patients before and after the release of CREATE-X and to assess factors associated with receiving NAC vs adjuvant chemotherapy (AC). Methods: The National Cancer Database was queried for women with cT1-2N0M0 TNBC from 2014–19. NAC utilization was collected and categorized as 2014-15 (pre-CREATE-X), 2016-17 (transition yrs), and 2018-19 (post-CREATE-X). Those who did not receive chemotherapy were excluded. NAC use over time was analyzed via multivariable logistic regression (MLR). Clinical and demographic factors associated with NAC vs AC utilization were assessed using ANOVA, Chi-squared, and Fisher Exact tests. A MLR model was used to determine predictors of receipt of NAC vs AC. Results: 55,633 women were treated from 2014-19: 26.9% with NAC, 52.4% with AC, and 20.7% received no chemotherapy (median ages 53, 59, and 71yrs, respectively, p < 0.01). Most had cT1c (32.7%, n = 18,190) or cT2 (41.95%, n = 23,331) tumors and 99% had invasive ductal pathology. NAC utilization significantly increased over time, 19.5% (n = 3,465 of 17,777) in 2014-15, 27.1% (n = 5,140 of 18,985) in 2016-17, and 33.6% (n = 6,337 of 18,871) in 2018-19 (p < 0.01). On MLR analysis, increased use of NAC was associated with younger age ( < 50yrs), non-Hispanic white patients, having no comorbidities, having a cT2 tumor, grade 2 disease, and care at an academic or integrated network cancer program (p < 0.05 for all). Patients with Medicare and Medicaid insurance were less likely to receive NAC (p < 0.01). Patients who traveled > 60 miles to their treating facility were more likely to receive NAC (p < 0.01). Conclusions: From 2014–19, NAC utilization increased for patients with cT1-2N0M0 TNBC coinciding with the release of the CREATE-X results. Findings demonstrate the significance of the multidisciplinary oncology team in developing individualized treatment plans based on emerging clinical trial evidence. Racial, socioeconomic, and access disparities were observed in NAC utilization and warrants further investigation and interventions to ensure equitable care. [Table: see text]
Magnetic resonance imaging tumor regression shrinkage patterns during neoadjuvant chemotherapy versus neoadjuvant immunochemotherapy in triple-negative breast cancer (NeoMDSS-TN-SP): A nonrandomized, prospective cohort study.
Authors: Zhang Liulu , Zou Jiachen , Chen Yuanqi , Yan Xinjian , Wang Kun
Published: June 2023

e12601

Background: Previous studies have shown that the tumor regression shrinkage pattern (SP) of triple-negative breast cancer (TNBC) during neoadjuvant chemotherapy (NAC) is more likely to present with concentric shrinkage (CS), which is associated with a pathological complete response (pCR). Since immunotherapy and chemotherapy have different antitumor mechanisms, it is reasonable to believe that there may be different SPs between neoadjuvant immunochemotherapy (NAIC) and NAC. This NeoMDSS-TN-SP prospective study aimed to investigate whether tumor SPs differed between NAIC and NAC in TNBC, as well as to calculate the correlation between SP and efficacy. Methods: In this prospective, single-center, nonrandomized cohort study, eligible patients with stage II-III TNBC received NAIC or NAC and underwent MRI at baseline, after the first cycle of neoadjuvant therapy, and preoperatively. Based on the MRI after the first cycle, the tumor SPs were grouped into three categories: CS, diffuse decrease, and no change or enlargement. The primary end point was the difference in SP between the two treatment groups. Secondary endpoints included the correlation between SP and treatment efficacy. This study is registered with ClinicalTrials.gov, number NCT04909554. Results: Ninety-nine patients were enrolled from January 2019 to July 2021; 65 received NAC and 34 received NAIC. Baseline characteristics were similar between the two groups. More patients in the NAIC group achieved pCR after surgery than in the NAC group (82.4% vs. 44.6%, p=0.0003). In the NAC group, more patients showed CS (53.8%), and patients with the CS pattern had a significantly higher pCR rate than those with diffuse decrease or no change/enlargement (65.7% vs. 21.7% vs. 14.3%, p=0.0007). In the NAIC group, although a higher proportion of patients showed diffuse decrease (67.6%), all three SP categories had relatively high pCR rates, so pCR was not correlated with SP (85.7% vs. 82.6% vs. 75.0%, p=0.9029). Conclusions: This is the first study to investigate the tumor regression SP of NAIC in TNBC patients. Compared to traditional chemotherapy, NAIC was more prone to diffuse regression, but the relatively high pCR rates had no correlation with the SPs during neoadjuvant therapy. Clinical trial information: NCT04909554 . [Table: see text]
Neoadjuvant pyrotinib plus trastuzumab, dalpiciclib, and letrozole for triple-positive breast cancer: A pilot trial.
Authors: Xue Jinqi , Niu Nan , Wang Shuo , Chen Guanglei , Qiu Fang , Zhao Yi , Xing Fei , Zheng Xinyu , Tu Wei , Li Ke , Zhao Hai , Tang Meiyue , Xu Qianshi , Liu Chao , Zhao Yafei , Jiang Xiaofan , Huo Shiwen , Pang Zheng , Zhang Dianlong , Liu Caigang
Published: June 2023

e12603

Background: Our previous MUKDEN 01 study showed a promising total pathological complete response (tpCR) rate of 30.4% with neoadjuvant pyrotinib plus dalpiciclib (cyclin dependent kinase 4/6 inhibitor) and letrozole in patients with triple-positive breast cancer (TPBC), but the efficacy still needs improvement. This pilot study explored the efficacy and safety of adding trastuzumab to this neoadjuvant regimen in TPBC. Methods: Patients received five 28-day cycles of pyrotinib (320 mg once daily), dalpiciclib (125 mg once daily on days 1-21) and letrozole (2.5 mg once daily), plus six 21-day cycles of trastuzumab (8 mg/kg loading dose followed by 6 mg/kg maintenance dose on day 1), followed by surgery. The primary endpoint was tpCR (ypT0/is, ypN0) rate. Secondary endpoints were objective response rate (ORR), breast pathological complete response (bpCR; ypT0/is) rate, residual cancer burden (RCB), change in Ki-67 level from baseline to surgery, and safety. Results: Between February 16, 2022 and June 2, 2022, 12 patients were enrolled. Seven (58%; 95% CI, 27.7-84.8) patients achieved tpCR and bpCR. The rate of RCB 0-I was 75% (95% CI, 46.8-91.1%). ORR was 92% (95% CI, 64.6-98.5%). Mean Ki-67 level was significantly reduced from 45.0% (95% CI, 19.5% - 70.5%) at baseline to 17.2% (95% CI, 0.7% - 33.7%) after neoadjuvant therapy (P<0.05). The most common grade 3 adverse events were diarrhea (4 [33%]) and decreased neutrophil count (3 [25%]). No grade 4 events or treatment-related deaths occurred. Conclusions: This four-drug neoadjuvant regimen shows promising pathological response in patients with TPBC, with an acceptable safety profile. The results warranted further validation. Clinical trial information: NCT05228951 .
Neoadjuvant stereotactic body radiotherapy plus dalpiciclib and exemestane for hormone receptor-positive, HER2-negative breast cancer.
Authors: Niu Nan , Cao Shuo , Chen Guanglei , Xue Jinqi , Zhang Yu , Xu Yongqing , Yin Jianqiao , Liu Chao , Jiang Xiaofan , Tang Meiyue , Xu Qianshi , Jia Mingxuan , Zhang Xu , Zhang Zhenyong , Li Huajun , Li Ailin , Liu Caigang
Published: June 2023

e12604

Background: Despite cyclin dependent kinase 4/6 (CDK4/6) inhibitors having revolutionized treatment for advanced hormone receptor (HR)-positive, HER2-negative (HR+/HER2-) breast cancer, it still has limited efficacy in the neoadjuvant setting. Preclinical studies have indicated radiotherapy followed by CDK4/6 inhibitors can enhance antineoplastic effects. Stereotactic body radiotherapy (SBRT) is more effective than conventional fractionation. This MUKDEN 03 pilot study aimed to explore the efficacy and safety of a chemotherapy-free neoadjuvant regimen with SBRT followed by CDK4/6 inhibitors and endocrine therapy in patients with HR+/HER2- breast cancer. Methods: In this single-center, single-arm prospective study, treatment-naïve patients with unilateral invasive, pathologically confirmed HR+/HER2- breast cancer at stage II-III would be enrolled. Eligible patients received neoadjuvant SBRT (24Gy/3f) to breast target lesion followed by dalpiciclib (150mg daily for 3 weeks on and 1 week off) and exemestane (25mg daily) every 4 weeks for 6 cycles. Patients without menopause also received goserelin 3.6 mg every 4 weeks. The primary endpoint was the proportion of patients with residual cancer burden (RCB) score of 0-I. Key secondary endpoints included objective response rate (ORR), pathologic complete response (pCR), and safety. Results: Between November 2021 and August 2022, 12 enrolled patients completed the study treatment and surgery. The median age was 48.5 years (95% confidence interval [CI], 36-56) and half of them were premenopausal women. 5 (41.7%) patients had stage III disease. The results met the primary endpoint as the therapy resulted in RCB 0-I of 16.7% (2/12, 95% CI 3.5%-46.0%) with the ORR of 91.7% (11/12, 95% CI 62.5%-100%). 2 (16.7%, 95% CI 3.5%-46.0%) patients achieved pCR in the breast and axilla (ypT0/is ypN0). 3 (25.0%, 95% CI 8.3%-53.9%) patients reached pCR in the breast (ypT0/is). The most common grade 3 adverse events (AEs) were neutropenia (8 [66.7%]) and leukopenia (3 [25%]). No patient experienced grade 4-5 AE or death. There was no patient with radiation-related dermatitis and skin hyperpigmentation. Conclusions: Neoadjuvant SBRT followed by dalpiciclib and exemestane seems effective and tolerable, which may offer an alternative for patients with HR+/HER2- breast cancer. The results warranted further validation. Clinical trial information: NCT05132790 .
Efficacy and safety of neoadjuvant double anti-Her2 blockade combined with anthracycline-free chemotherapy in locally advanced breast cancer.
Authors: Rodriguez Garcés Maria Yeray , Samblás Victoria García , Morales Pancorbo David , Bayo Calero Juan Lucas
Published: June 2023

e12612

Background: Double anti-Her2 blockade combined with chemotherapy (CT) is a standard regimen in Her2 positive locally advanced breast cancer (LABC) with a high risk of relapse. TCHP provides more anti-Her2 treatment, better pathological complete response (pCR) rates and less cardiotoxicity. However, it is not a very widespread option due to the risk of toxicity. Our group shows a manageable toxicity profile by adding G-CSF as primary prohylaxis. Methods: We describe our experience with neoadjuvant TCHP and pegfilgrastim combination between years 2017-2023. Efficacy and safety were analyzed and compared with other schemes accepted by clinical guidelines. Results: 62 patients, median age 48 years; 61.3% were premenopausal; 54.8% were stage II at diagnosis and 45.2% were stage III; 67.7% had N+; 62.9% had RH-. A total of six cycles were completed in 85.5%; 8 patients discontinued treatment due to toxicity. The most frequent adverse events were hematological (grade 3-4 in 8.1%) and digestive (grade 3-4 in 19.4%). No cardiac event was reported. 6.5% were hospitalized due to toxicity (3.2% febrile neutropenia). Dose reduction was needed in 43.5%. Clinical response occurred in 98.4% and radiological response in 87.1% (complete in 38.7%). pCR (ypT0/isN0) was obtained in 67.7% (66.7% in N+; 77.4% in RH-). Up to now, 4 patients have relapsed (3 of them had pRC) and 3 have died. After median 24.5 months of follow-up, the median relapse-free and overall survival by Kapplan-Meier have not been reached. Cox regression shows that getting rPC does not impact survival. The Odds Ratio shows a higher proportion of obtaining pRC in the RH- and N+ subgroups, but without statistically significant differences. Conclusions: Our data based on combination of TCHP and pegfilgrastim shows considerable efficacy with an acceptable toxicity profile. The main advantage is the intensification of double lock dose, without anti Her2 window period, avoiding the addition of anthracyclines and, therefore, cardiac toxicity. pRC and toxicity profile results were better than other regimen proposed in other studies. Our data shows that pRC has no impact on survival. We assume a favorable association between pRC and N+ and HR-, although not statistically significant, probably due to the small amount of patients. Based on these favorable results, we believe that the priority use of TCHP-GCSF should be considered in the neoadjuvant treatment of Her2+ LABC. [Table: see text]
Neoadjuvant tucidinostat combined with chemotherapy for hormone receptor-positive, HER2-negative breast cancer.
Authors: Niu Nan , Xue Jinqi , Qiu Fang , Chen Guanglei , Gu Xi , He Guijin , Cao Shuo , Yu Xiaopeng , Xu Yongqing , Yin Jianqiao , Han Sijia , Han Ye , Tang Meiyue , Zhao Yafei , Zheng Ran , Zheng Xinyu , Xu Hong , Liu Caigang
Published: June 2023

e12617

Background: Both neoadjuvant chemotherapy and endocrine therapy only result in trivial pathological complete response rates and moderate objective response rate (ORR) in hormone receptor (HR)-positive, HER2-negative breast cancer, more promising alternatives are urgently needed. Tucidinostat is an oral subtype-selective histone deacetylase inhibitor that has shown efficacy and safety when used in combination with exemestane in patients with advanced HR+ breast cancer. This MUKDEN 05 study aimed to assess the efficacy and toxicity of the combination of tucidinostat and EC-T as a neoadjuvant strategy in patients with HR+/HER2-, stage II-III breast cancer. Methods: This study is a multicenter, single-arm, phase II study. Eligible patients received 20 mg tucidinostat orally twice a week (on days 1, 4, 8, and 11), 2 weeks on, 1 week off. The dose and administration schedule of EC-T were as follows: 4 cycles of epirubicin 90 mg/m2 and cyclophosphamide 600 mg/m2 every 3 weeks, followed by 4 cycles of docetaxel 100 mg/m2 every 3 weeks. The primary endpoint was the proportion of residual cancer burden (RCB) 0-I. Key secondary endpoints included pathological complete response (pCR), objective response rate (ORR), and safety. Results: Between May 2022 and August 2022, a total of 35 patients were enrolled. 27 patients were pathologically evaluable. The remaining 8 patients have completed neoadjuvant treatment and wait for operation. The ratio of RCB 0-I was 37% (95% CI, 23.2-53.7%). ORR was 86% (95% CI, 70.6-93.7%). Four (15%; 95% CI, 5.91-32.5%) patients achieved bpCR, and one (4%; 95% CI, 0.67-18.3%) patients achieved tpCR. Most adverse events (AEs) were grade 1 or 2. Grade 3/4 AEs included neutropenia (21.1%), and thrombocytopenia (15.8%). Conclusions: The combination of Tucidinostat and EC-T had an acceptable safety profile and encouraging clinical responses, offering a neoadjuvant treatment option for patients with early HR+/HER2- breast cancer. Further research is required to validate these findings. Clinical trial information: NCT05400993 .
Comparing time to treatment for neoadjuvant chemotherapy for breast cancer across the urban-rural continuum.
Authors: Kasper Laura , Coogan Alison , Akers Rachel , Lunt Lilia , Madrigrano Andrea , Dixon Matthew , O'Donoghue Cristina
Published: June 2023

e12619

Background: Time-to-treatment is a quality measure in breast cancer care that can impact breast cancer survival as delayed treatment can increase mortality. This study aims to determine whether differences exist in time-to-treatment for breast cancer patients receiving neoadjuvant chemotherapy (NAC) across the urban-rural continuum. Methods: The National Cancer Database (NCDB) was queried for women with a diagnosis of breast cancer between 1 January 2004 – 31 December 2019. Patients who fit criteria for NAC consideration according to NCCN guidelines were included (inflammatory breast cancer, HER2 positive with tumor stage >T1c, triple negative with tumor stage >T1c, HER2 positive or triple negative lymph node positive, and stage III estrogen receptor (ER) positive). Analysis was stratified according to histopathologic subtype and geographic location as defined by the NCDB. Differences were analyzed using χ2 tests. Results: For patients with NAC-eligible breast cancer, there was no statistically significant difference in terms of days until treatment for each histopathologic subtype across the urban-rural continuum. The distance to treatment facility increases the further away patients are from a large metropolitan area, with individuals located in an urban area that is not adjacent to a metro area traveling the furthest distance (12.7mi large metro, 18.1mi small metro, 36.7mi urban adjacent to metro, 62.6mi urban not adjacent to metro, 56.4mi rural). No significant difference in distance traveled was observed between tumor subtype group. Conclusions: While previous studies have determined that rural patients receive NAC at lower rates than those in large urban areas, this study shows that time to treatment and distance traveled is similar across rural urban continuum and different histopathologic subtypes. Future studies are needed to determine why patients receive NAC at lower rates in rural areas.