bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of pre-treatment hemoglobin levels with survival outcomes among Indian women with triple negative breast cancer.
Authors: Sagiraju Hari Krishna Raju , Gogia Ajay , Sharma Rakesh Kumar , Deo S.V.S. , Sharma Dayanand , Gupta Ritu , Mathur Sandeep
Published: June 2022

e12549

Background: Prevalence of Triple Negative Breast Cancer (TNBC), which has utterly poor prognosis and higher recurrence rate, is high among Indian women ranging from 20-43% across different regions of India. Previous studies from other countries have shown that pretreatment hemoglobin and hematocrit values influence treatment outcomes among breast cancer patients. Recent 2019-2020 National Family Health Survey (NFHS) of India reported that 66.4% of women suffer from anemia. This study examined the association of pre-treatment hemoglobin levels with survival outcomes among Indian women with TNBC. Methods: We retrospectively analyzed the medical records of 435 women registered at our institute with a diagnosis of TNBC between the years 2013-2021. Pre-treatment hemoglobin levels i.e. either before the start of neoadjuvant chemotherapy (NACT) or prior to surgery among those who received adjuvant chemotherapy were retrieved from the medical records along with clinical and tumor characteristics. Primary outcomes were relapse free survival (RFS) and overall survivals (OS). Cox-regression and Kaplan-Meier survival analysis were used to examine the association of pre-treatment anemia with survival outcomes in these patients. Results: Fifty-one percent (n=221) of the 435 TNBC patients in our study cohort had pretreatment hemoglobin level of <12.0 g/dL (based on the World Health Organization criteria). 278 patients received NACT and pathological complete response (pCR) rates were similar in anemic (31.5%) and non-anemic groups (30.1%). When adjusted for clinical and other hematological parameters, anemia was not associated with pCR. Median follow-up of the study cohort was 22.9 months (Range: 2.6 to 92.7 months). Pre-treatment anemia was significantly associated with poor RFS when adjusted for clinical and hematological parameters [adjusted Hazard ratio (aHR) (95%CI): 1.53 (1.02-2.31)]. Median RFS was 52.5 months among the anemic group and was not reached in non-anemic group. Effect of anemia on RFS did not vary by age category or menopausal status. However, the effect of anemia on OS varied significantly by menopausal status. Menopausal women with anemia at time of diagnosis had significantly higher hazard of death compared to menopausal women without anemia [aHR (95%CI): 5.0 (1.15-21.66)] and this association was not observed in pre-menopausal women [aHR (95%CI): 0.53 (0.19-1.44)]. Conclusions: Pretreatment hemoglobin level of <12g/dL was associated with poor survival outcomes among Indian women with TNBC and the effect of anemia on overall survival of these patients varied by menopausal status. Evaluation of hemoglobin levels during chemotherapy, pre-post surgery, and at various stages of follow-up is needed to determine the independent association of hemoglobin level trajectories with treatment outcomes and long-term survival among these TNBC patients.
CD45-positive tumor infiltrating lymphocytes in early-stage hormone-positive, HER2-negative (ER+/HER2-) breast cancer: Correlation with proliferation and prognostic signature scores.
Authors: Lucas Mairi , Kinsella Zak , Gonzalez Claudia Aura , Hurley Camille , Blümel Anna , Fay Joanna , O'Grady Anthony , Murphy Verena , Jahangir Chowdhury Arif , Burke Caoimbhe , Rahman Arman , Crown John , Kelly Catherine Margaret , Gallagher William M. , O'Connor Darran
Published: June 2022

e12555

Background: Tumour infiltrating lymphocytes (TILs), have been associated in higher responses to treatment and are thought to be a prognostic marker in a number of cancer types. The role of TILs in breast cancer varies depending on the molecular subtype of the disease. In hormone positive, HER2-negative breast cancer, the significance of TILs is less clear, partly due to the paucity of data in this area. We aim to assess overall TILs in early-stage, hormone-positive, HER2-negative (ER+/HER2-) breast cancer and its relationship with proliferation index, Ki67, and the 21-gene recurrence score. Methods: Archival patient tissue samples of early-stage, ER+/HER2- breast cancer from the Irish arm of the TAILORx clinical trial were used. Full-face sections of these tumours were stained with anti-CD45 antibody (DAKA clone M0701) via the automated Leica Bond III system. A watershed cell-detection algorithm from the open-source digital pathology software, QuPath, was fine-tuned to identify true cell objects and positive immune markers. Optimised detection parameters were used to calculate the percentage of overall CD45+ cells (CD45%) within the tumour area. Patient TIL categories were dichotomised into High v Low CD45%, with 10% chosen as the threshold. CD45% was further correlated with proliferation index, clinical data, and 21-gene recurrence score. Results: 409 samples were included in the analysis. The mean CD45% was 5.96, with samples ranging from 0.13 to 78.86. The majority of samples were in the range of 0-10% of CD45% positivity with 89% (n = 367) patients in this category. Stratification of the cohort by 21-gene-recurrence score (RS) into Low, Intermediate and High, showed a statistically significantly high CD45% in patients with a High RS compared to Low RS (p = 0.0015). When divided by recurrence score group, high CD45% trended toward a lower disease free survival (DFS) when compared to low CD45%, with statistical significance found in those in the Intermediate RS chemotherapy treatment arm (p = 0.009). Conclusions: The role of TILs in ER+/HER2- breast cancer is still undefined. While a High RS was associated with a higher percentage of CD45-positive lymphocytes, the impact on recurrence and response to treatment remains unclear. Further studies to assess the role of different tumour infiltrating lymphocyte phenotypes, and the spatial distribution of assessed markers, are needed.
Prognostic value of circulation tumor DNA dosing in patients in neoadjuvant breast neoplasia (GIRO-ctDNA).
Authors: Giro Camila , Cruz Felipe Melo , De Rêgo Barros Lilian Arruda , Fonseca Fernando Luiz Affonso , Del Giglio Auro , Yamada Alayne Magalhaes Trindade Domingues
Published: June 2022

e12559

Background: Pathologic Complete Response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer is strongly associated with a favorable prognosis. We evaluated whether there is a correlation between serum levels of circulating tumor DNA (ctDNA) during neoadjuvant therapy with obtaining pCR and detection of residual disease after treatment. Methods: ctDNA was isolated from 310 plasma samples of 27 patients diagnosed with localized and/or locally advanced breast cancer treated with standard NAC alone or combined with immunotherapy and/or anti-HER 2- targeted therapy when indicated. Blood was collected at pretreatment, every 15 days during treatment and before surgery. Results: Eight (29%) of the 27 patients presented pCR, 4 triple negative (50%, 3 HER2+ (37%) and 1 (13%) luminal B. We observed that throughout the neoadjuvant treatment in the seventh collection the ctDNA levels were significantly higher in patients who did not presented pCR in relation to those who achieved it, p-value = 0.014. 62% of patients who presented pCR in the surgical specimen also had a complete radiological response, with a significant correlation, p-value = 0.02492. Although we did not find statistical significance, we did note that patients who presented pCR had a tendency towards an initial increase in their ctDNA levels after the first cycle of chemotherapy. Conclusions: ctDNA dosage in the third month (seventh collection) of neoadjuvant treatment is inversely correlated with the achievement of tumor pCR. The tendency we saw of an increased ctDNA levels soon after the initiation neoadjuvant chemotherapy could indicate tumor sensitivity by the increase in cell death with release of ctDNA into the circulation. Clinical trial information: NCT05050890.
Study of the level of tumor markers and mutations in the BRCA1/2 genes in breast cancer patients with metachronous tumors.
Authors: Kamishov Sergey Viktorovich , Izrailbekova Kamila Shavkatovna , Balenkov Oleg Yurievich
Published: June 2022

e12563

Background: Primary multiple malignant tumors are more common in women with breast cancer (BC). However, the difference in the frequency of mutations in the BRCA1/2 genes in metachronous BC tumors has not been fully studied, and there are also conflicting data on the increase in the level of specific tumor markers in this category of patients. Methods: The survey included 58 patients with BC with II-III clinical stages of the disease, of which metachronous tumors in terms of 6 months or more were found in 26 (44.8%) patients, among them metachronous cancer of the second breast - in 14 (53 .8%), cancer of the body of the uterus - in 7 (26.9%) and ovarian cancer - in 5 (19.2%) patients. In the control group of 32 (55.2%) patients with initially diagnosed BC, with the same stages of the disease. Tumor markers were determined in the peripheral venous blood of patients using reagent kits for ELISA analysis produced in Russia. The study of mutations in the BRCA1/2 genes was performed using sequencing on the Illumina MiSeq platform in tumor samples from waxed histological blocks. Library sequencing was performed using MiSeq Reagent Kit v2. Results: ELISA analysis of the level of tumor markers in patients with BC showed that with the development of metachronous cancer, the studied markers were more common than in the control group. In patients with metachronous tumors, elevated levels of CA-125 occurred in 10 (38.5%) patients, CA-15-3 - in 8 (30.8%), CA-19-9 - in 4 (15.4%), AFP - in 5 (19.2%), CEA - in 6 (23.1%). In the control group, CA-125 was found in 6 (18.8%) patients, CA-15-3 - in 5 (15.6%), CA-19-9 - in 2 (6.3%), AFP - in 1 (3.1%), CEA - in 2 (6.3%). Excess levels significant for diagnosis were observed for CA-125 and CA-15-3 in both groups of patients, but in the group of patients with BC with metachronous tumors, these figures were approximately 2 times higher. In the rest of the patients, the oncomarkers under consideration did not reach values significant for diagnosis. The total incidence of patients with clinically significant germline variants in the BRCA1/2 genes in the control group was 5 (15.6%), of which there were predominantly patients with an increased frequency in the population (5382insC, 4154del4, C61G). The total incidence of BC patients with metachronous tumors with germline and somatic variants in the BRCA1/2 genes was 16 (61.5%), with an increased frequency in the same population, mainly in patients with germline mutations. Conclusions: Dynamic study of the level of tumor markers CA-125 and CA-15-3 and CA-19-9 may be useful in the preventive examination of patients with a history of BC as an early diagnosis of the development of metachronous tumors in this category of patients. The most important diagnostic unfavorable factor in the development of metachronous tumors in the examined BC patients was germline mutations in the BRCA1/2 genes.
Gene expression profiling for breast cancer in the Philippines: Real-world data on feasibility, possible disparities, and clinical implications for LMICs.
Authors: Kho Markyn Jared Ngo , Kho Mark Richard
Published: June 2022

e12569

Background: Racial, biological and socioeconomic disparities have most recently been shown to impact on specific molecular subtypes of breast tumorsand on its clinical implications including the decision to omit adjuvant chemotherapy. Despite considerable logistical and cost constraints, we provide the first-ever documented and tangible profile of gene expression of breast cancers in the Philippines for a better understanding of its role in facilitating future testing and health policy making in an LMIC setting. Methods: This is a case series review of the 70-gene (MammaPrint) and 80-gene (BluePrint) signature done among Filipino patients from Dec 2013 to Nov 2021. Data on demographics, tumor characteristics, adjuvant therapy received and clinical risk assessment in the MINDACT study to c-low or c-high were gathered and analyzed. Results: Thirty-six females aged 36-75 years with invasive breast carcinoma Stage I to IIB had the following profile: Low Risk Luminal A (19, 52.8%), High Risk Luminal B (7, 19.4%), High Risk Her-2 (3, 8.3%), High Risk Basal (7, 19.4%). All low-risk patients underwent adjuvant endocrine therapy alone thus foregoing otherwise clinically recommended chemotherapy. No significant trend (in age, laterality, tumor grade and stage) can be discerned within all stratification groups except in the following areas: Histology: low risk profile in lobular carcinoma (n=2) Tumor Size: high risk profile in all tumors measuring 4.1 – 5 cms (n=4) Nodal Status: low risk profile in 6 of 8 patients with node+ disease LVI among node- patients: low risk profile in all 6 LVI+ tumors HR status: high risk profile in all 7 tumors with HR- status Her-2 neu status: good IHC test correlation with genomic subtype HR and Her-2 neu status: HR+her2- status in all 19 low risk tumors while high risk basal subtype in all 5 HR-her2- or triple-negative (TNBC) tumors Clinical risk in MINDACT: low genomic risk in 11 of 25 (44%) c-high patients.

Conclusions: Gene profiling of breast cancer in a resource-limited setting is feasible and imperative to avoid chemotherapy and/or overtreatment. Clinically relevant disparities may exist which in turn can affect outcomes, decisions and health policies in adjuvant therapy and overall cancer care.[Table: see text]
Analysis of non-sentinel lymph node status on 10-year overall survival among patients with breast cancer and sentinel lymph node metastasis.
Authors: Lei Huizi , Yuan Pei , Xu Binghe , Ying Jianming
Published: June 2022

e12584

Background: To investigate retrospectively the effect of non-sentinel lymph node status (non-SLN) on 10-year overall survival (OS) and non-SLN metastasis risk factors in patients with breast cancer and sentinel lymph node (SLN) metastasis. Methods: A large population (n = 15510) underwent SLN dissection in Cancer Hospital, Chinese Academy of Medical Sciences from 2011 to 2022. In total, 3033 (19.6%) cases had at least one SLN metastasis, which underwent axillary lymph node (ALN) dissection. The clinicopathological characteristics and their relationship with non-SLN status were analyzed. Among patients from 2011-2012(n = 132), the effect of non-SLN status on 10-year OS and disease-free survival (DFS) with SLN metastasis were also analyzed. Results: In 3033 patients with SLN metastasis, the mean age was (50.42±10.59) years. The average number of SLN metastasis in each patient was 1.75±1.21, the average number of SLN detected was 4.89±2.03 and the average number of ALN removed was 22.36±8.88. The number of SLN metastasis≥2 and positive lympho-vascular invasion were risk factors of non-SLN metastasis ( P< 0.05), but not the age, T stage and histological grade. In 132 patients from 2011-2012, a median follow-up of 9.1 years (interquartile range, 7.3-9.5 years), the non-SLN metastasis occurred in 60 cases (45.5%), DFS 70.8%, OS 85.9%; non-SLN non-metastasis occurred in 72 cases (54.5%), DFS 85.6%, OS 90.4%. There was no significant difference between two groups in DFS(χ² = 0.61, P = 0.43) and OS (χ² = 0.06, P = 0.81). Conclusions: The number of SLN metastasis≥2 and positive lympho-vascular invasion were risk factors of non-SLN metastasis. There were no significant differences between non-SLN metastasis group and non-metastasis group in DFS and OS.
Survival trends of patients with Paget disease of the breast: A National Cancer Database (NCDB) study.
Authors: Truong Gia Thinh , Creech Zachary , Denny Regan , Hu Robert W. , Verplancke Kiana , Silberstein Peter T. , Tupper Connor
Published: June 2022

e12585

Background: Paget disease of the breast is a malignant tumor that comprises only 1-3% of all breast carcinomas. It may coexist with an underlying ductal carcinoma in situ or present alone without additional carcinomas. Due to the rarity of this carcinoma and minimal literature available, we intend to identify potentially important prognostic factors, particularly those of socioeconomic origin. Methods: We performed a retrospective investigation of 5,918 patients diagnosed with Paget Disease of the breast from the NCDB between 2004-2018. Patient demographic and clinical characteristics such as household income, insurance status, treatment center type, and treatment center location were extracted from the database. Survival rates were compared using Kaplan-Meier curves, log-rank test, univariate and chi-square analysis. Data were analyzed using SPSS statistics 27. Results: African American patients had higher mortality rates than Caucasian patients (p < 0.005). Patients with underlying intraductal carcinoma of the breast had the highest survival rates (p < 0.001). Patients who received immunotherapy as part of the treatment plan had a significantly higher survival rate than those who did not (136.97 vs. 144.24 months respectively, p < 0.001). Patients coming from lower median household incomes had significantly lower survival rates. Specifically, patients with a household income of less than $38,000 had a lower mean survival rate compared to those with a household income of greater than $63,000 (122.74 months compared to 140.63, respectively, p < 0.001). Those with private insurance had a higher mean survival time than those with Medicaid and no insurance (170.60, 138.13, and 130.69 months respectively, p < 0.001). Patients from counties in metro areas with populations of 1 million or more had a significantly higher survival rate than those from counties in metro areas with less than 1 million (p < 0.003). In addition, patients treated at academic centers had a higher mean survival rate than those treated at non-academic centers (p < 0.001). Conclusions: Our results show significant variation in survival rates among patients based on their socioeconomic and treatment center characteristics. Additional research targeting patients with these characteristics can lead to improved clinical outcomes.
Patterns of care and survival outcomes for young women treated for early breast cancers in a community hospital system.
Authors: Thet Aye , Hadid Tarik H. , Boura Judith , Gohel Narendra , Falk Jeffrey , Vlachaki Maria T. , Jay Allison , Chuba Paul J.
Published: June 2022

e12586

Background: Younger women with breast cancer have relatively poor prognosis and higher rates of locoregional recurrence. Epidemiologic data suggest equivalent survival with mastectomy or breast conserving surgery (BCS) in this population. We analyzed patterns of care and survival outcomes for women aged < 45 years with breast cancer treated at Ascension Macomb Oakland Hospital (AMOH), Ascension St John Hospital (ASJH), and Ascension Providence Hospital (APH). Methods: Between 2006 and 2015 there were 4703 patients treated for breast cancers at AMOH, ASJH, and APH. We identified a subset of 319 patients aged < 45 treated for breast cancers and investigated patients' tumor characteristics, type of surgery, and overall survival by using the Metric database and reviewing patient charts. Kaplan-Meier analysis and log-rank tests together with univariate analysis was done by using SAS for Windows 9.4. Results: With median follow-up of 53 months among living patients, 26 patients had died. African American race was associated with decreased overall survival (log-rank p=0.0031). Factors associated with improved overall survival included AJCC stage grouping (p=0.009), estrogen receptor (p=0.0004) or progesterone receptor positivity (p=0.005), or HER2 negativity (p=0.039). Similarly, survival was different according to grouping cases as luminal A (n=174), luminal B (n=39), basal (n=46), HER2 (n=23) and unknown phenotype (n=37) (P=0.008). Considering all cases 91 were treated with BCS (28.5%) and 228 with mastectomy (71.4%; 113 unilateral and 115 bilateral with or without reconstruction). Conclusions: In this group of young women, overall survival was influenced by stage and breast cancer phenotype as expected. African American race was associated with inferior overall survival. We found high rates of mastectomy with or without reconstruction. In the future comprehensive disease profiling will help to direct decision making.
Characteristics of cytokine profile of wound fluid in breast cancer patients after mammoplasty with textured implants.
Authors: Przhedetskaya Viktoria Yu , Sagakyants Aleksandr B. , Przhedetskiy Yuriy V. , Zlatnik Elena Yu , Shulgina Oksana G. , Zolotareva Ekaterina I. , Ulianova Elena P. , Bondarenko Elena S. , Pozdnyakova Viktoria V. , Ulianova Yulia V. , Volkova Viktoriya L. , Bauzhadze Mamuka V. , Pustovaya Irina V. , Chertova Natalia A. , Goncharova Elena G. , Maldonado Mary L. , Vladimirova Liubov Yu
Published: June 2022

e12589

Background: Breast reconstruction after mastectomy for breast cancer (BC) is an important rehabilitation stage. Breast prosthesis implantation is sometimes accompanied by different complications which can be influenced by the immune system status. The aim of this study was to identify characteristics of the local cytokine profile in patients with breast cancer in the early postoperative period after reconstructive surgery with textured implants (TI). Methods: The study included 30 patients aged 32-68 years, mean age 42.9±1.98 years, with stage I-IIb BC (monocentric nodular BC, T1N0M0 - T2N1M0). All patients underwent skin-sparing mastectomy with level II axillary lymph node dissection and immediate implant reconstruction in 2017-2019. Levels of cytokines IL-1β, IL-2, IL-4, IL-6, IL-8, IFN-γ, and TNF-α were determined by ELISA in wound fluid from the cavity with TI on days 1, 3-4 and 7 after the surgery. Results: Levels of IL-6 in wound fluid of patients with TI statistically significantly decreased by 43% (p=0.036) and 41% (p=0.039) on days 3-4 and 7 after the surgery, and IL-2 decreased by 27% (p=0.045) with its further increase by 44% (p=0.037) compared to day 1. A pronounced increase of the IFN-γ levels by 118% (p=0.018) and 158% (p=0.012) was registered respectively on days 3-4 and 7 after surgery. Conclusions: Reconstructive surgery with TI is followed by a local increase in levels of IL-2 and IFN-γ which may indicate increasing antitumor potential of the microenvironment. The revealed decrease in IL-6 levels after TI implantation indicates certain features of the inflammatory reaction development in the intervention site.
Integrated tumor genomic and immune microenvironment analysis identifies predictive biomarkers associated with the efficacy of neoadjuvant therapy for triple-negative breast cancer.
Authors: Zhu Yanhui , Pan Chaohu , Zhang Hongfei , He Gao , Yu Xiafei , Cui Xiaoli , Yang Junzhe , Zhang Xiaoqiang , Gao Edmond , Liu Xiaoan
Published: June 2022

e12592

Background: Although neoadjuvant chemotherapy (NAC) is currently the best therapy for triple-negative breast cancer (TNBC), resistance still occurs in a considerable proportion of TNBC patients, making it crucial to understand resistance mechanisms and identify predictive biomarkers for patient selection. Methods: Biopsy samples were collected from 21 patients with TNBC who underwent NAC. Whole-exome sequencing, targeted sequencing, and multiplex immunohistochemistry (mIHC) were carried out on the all clinical samples and used to identify and validate potential biomarkers associated with response to NAC. In addition, data on 190 TNBC patients who had undergone chemotherapy were obtained from The Cancer Genome Atlas (TCGA) and analyzed to further validate our findings. Results: Both the tumor mutational burden (TMB) and tumor neoantigen burden (TNB) were significantly higher in responders than in non-responders. Higher response rates and longer survival rates were observed in patients with higher TMB. Patients with higher ratios of CD8 to M2 macrophages had higher response rates and improved survival rates. Finally, integrated analysis demonstrated that the combination of TMB and the ratio of CD8 T cells to M2 macrophages could further distinguish responders from non-responders in both enrolled patients and from public data. Conclusions: The findings of this study indicated that the combination of TMB and the ratio of CD8 T cells to M2 macrophages may be a potential biomarker for improving the recognition of NAT responders, thereby providing a basis for developing precision NAT regimens.
Dose-dense neoadjuvant chemotherapy in triple-negative breast cancer: Real-world data from a developing country.
Authors: Sharma Rakesh Kumar , Gogia Ajay , Sagiraju Hari Krishna Raju , Deo S V Suryanarayana , Sharma Dayanand , Mathur Sandeep
Published: June 2022

e12594

Background: Dose-dense adjuvant chemotherapy has been shown to be associated with improved long-term survival outcomes in triple-negative breast cancer (TNBC). However, there is a lacuna of data on the benefits of dose-dense neo-adjuvant chemotherapy (NACT) in TNBC particularly with respect to pathological complete response (pCR) rates and with the relapse or overall survival. To our knowledge no studies have been reported regarding the use or benefit of dose-dense NACT (ddNACT) over conventional NACT (cNACT) among Indian women with TNBC. Methods: This retrospective study included, 217 newly diagnosed cases of TNBC, treated with sequential anthracycline and taxane based NACT followed by definitive surgery. Study groups consisted of 137 patients who received 3-weekly conventional chemotherapy (cNACT group) and 80 patients with 2-weekly dose-dense NACT (ddNACT group) with granulocyte-colony-stimulating factor (GCSF) prophylaxis. Primary endpoint of the study was pathological complete response (pCR) rate and secondary endpoints were relapse-free survival (RFS), overall survival (OS) and grade-3/4 chemotoxicities. Fisher’s exact test was used to compare pCR rates. Kaplan-Meier and cox regression survival analysis were used to compare survival outcomes. Results: Median age (Interquartile range) in overall population, cNACT and ddNACT group were 43 (37-50), 44 (37-50) and 42 (36.5-48) years respectively. Baseline parameters were comparable between study groups, except that ddNACT group had higher proportion of premenopausal patients as compared to cNACT group (72.5% vs 55.5%). Majority of the patients presented at advanced stage, with stage-III being predominant, constituted by 97 (70.1%) and 55 (67.5%) patients in cNACT and ddNACT group respectively. No significant difference in pCR rate (32.8% vs 31.3%; p=0.808) was observed across the study groups. In multivariate analysis, dose-dense chemotherapy was no better than conventional chemotherapy for achieving pCR (Odds ratio [OR]: 0.86, 95% confidence interval [CI]: 0.45-1.63; p=0.639 and had no RFS advantage over conventional chemotherapy [Median RFS: Not reached in ddNACT vs 56.1 months in cNACT; Hazard Ratio: 0.83, 95% CI (0.48-1.44)]. OS was also comparable in both the groups with 3-year survival rate of 78.8% (95%CI: 60.9-89.2) in ddNACT group vs 84.3% (95% CI: 74.8-90.4) in cNACT group. Grade-3/4 toxicities were comparable in both groups. Conclusions: This observational study focusing on ddNACT among TNBC patients demonstrated similar pCR and toxicity rates with no significant survival benefits compared to cNACT regimen. Cost-benefits of frequent hospital visits for GCSF administration associated with dose dense therapy need further consideration before implementing such these regimens in lower-middle income countries.
Biomarker evolution after neoadjuvant systemic therapy in breast cancer.
Authors: Castillo Dan Ran , Pairawan Seyed Saeed , Denham Laura , Lum Sharon S. , Nagaraj Gayathri
Published: June 2022

e12615

Background: Tumor heterogeneity is one of the hallmarks of breast cancer (BC) and has major implications for treatment response and resistance. Currently, there are no specific guidelines regarding biomarker reassessment on residual tumor post-neoadjuvant systemic therapy (NAST). In this study, we compared biomarker discordance between pre- and post-NAST tumors at our institution and determined if actionable changes were observed. We also report the impact of the detected biomarkers differences on the choice of adjuvant treatment. Methods: We conducted a retrospective review of BC patients who received NAST followed by definitive surgery from 2004 to 2020. The initial tissue biopsies were tested for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status per ASCO/CAP guidelines and repeated on the residual tumor tissue after NAST. Descriptive statistics was used to compare clinicopathologic characteristics. The biomarkers were compared using Wilcoxon’s t test and McNemar’s test. Concordance analysis of intrinsic subtypes was evaluated by Cohen’s kappa method. Results: Out of 434 patients who undergone surgical resection following NAST, 95 (22%) patients were identified to have repeat biomarker testing of residual invasive BC post NAST. 30 out of the 96 patients were found to discordant receptor status on repeat biomarker testing. In this cohort of thirty patients with discordant biomarkers, median age was 51.5 (29-70 years), 33.3% cases had stage II, and 56.7% had stage III BC. 66.75 patients were ER positive and/or PR positive, 20% patients were HER2 positive with one triple positive, and 13.3% patients were triple negative on pre-NAST tumors. Majority of the retesting was performed on breast tissue (90%, n = 27). The biomarker change was noted in 11 out of 30 (36.7%) for ER, 12 out of 30 (40%) for PR, and 13 out of 30 (43.3%) for HER2 marker. Concordance analysis demonstrated that HER2 was the most prone to change (Cohen K = -0.003) from pre-NAST to post-NAST specimen, whereas ER (Cohen k = 0.26) and PR (Cohen k = 0.18) were less subject to change. Kappa assumes theoretical maximum value of 1 when pre- and post-NAST are in agreement, a negative value indicates a poor concordance. One third of patients with discordant biomarkers had additional adjuvant treatment. 8 out of 30 patients (26.7%) were started on adjuvant anti-HER2 therapy due to HER2 positivity on post-NAST tumors. After ER positivity was detected on residual BC tumors, 2 initial triple negative patients (6.7%) were initiated on adjuvant endocrine therapy. Conclusions: Biomarker discordance due to tumor heterogeneity is an increasingly recognized phenomenon. Given the prognostic and therapeutic implications of biomarker driven BC management, retesting biomarkers routinely after NAST on residual invasive tumor would be beneficial in this patient population.
Mastectomy and immediate prepectoral versus submuscular breast reconstruction after neoadjuvant chemotherapy: Our early experience.
Authors: Scardina Lorenzo , Moschella Francesca , Magno Stefano , Sanchez Alejandro Martin , Di Leone Alba , D'Archi Sabatino , Franco Antonio , Biondi Ersilia , Carnassale Beatrice , Di Micco Annalisa , Bria Emilio , Masetti Riccardo , Franceschini Gianluca
Published: June 2022

e12618

Background: Conservative mastectomy with immediate prosthetic breast reconstruction (IPBR) is an oncologically accepted technique that allows to improve aesthetic results and patient quality of life. Traditionally, implants have been placed in a submuscolar (SM) plane beneath the pectoralis major muscle (PMM). Recently, prepectoral (PP) placement of prosthesis is increasingly used in order to avoid morbidities related to manipulation of PMM. The aim of this study was to compare outcomes of SM vs PP IPBR after conservative mastectomy in patients with histologically proven breast cancer treated with neoadjuvant chemotherapy (NAC). Methods: In this retrospective observational study we analyzed two cohorts of patients that underwent mastectomy with IPBR after NAC in our Istitution from January 2018 to December 2021. Conservative mastectomy was performed in 155 of the 400 patients that underwent NAC during the study period. Patients were divided in 2 groups based on the positioning of implants: 60 SM versus 95 PP. Results: The two cohorts were similar for age (mean age 45 and 42 years in the SM and PP group respectively) and follow‐up (32 and 21 months, respectively). Mean operative time was 55 minutes shorter in the PP group (298 and 243 minutes in the SM and PP group). No significant differences were observed in overall major complication rates. Implant loss occurred was observed in 1.6% of patients (1/60) in the SM group and 1,05% of patients (1/95) in PP group. No differences were observed among the two groups in local or regional recurrence. Conclusions: Our preliminary experience, that represents one of the largest series of PP-IPBR after NAC at a single Institution documented in the Literature, seems to confirm that PP - IPBR after NAC is a safe, reliable and effective alternative to traditional SM - IPBR with excellent aesthetic and oncological outcomes; it is easy to perfom, reduces operative time and minimizes complications related to manipolation of PPM. However this promising results need to be confirmed in prospective trials with longer follow-up.
Neoadjuvant pegylated liposomal doxorubicin (PLD) plus cyclophosphamide followed by nab-paclitaxel (Nab-P) as primary chemotherapy continuously combined with dual HER2 blockage for HER2-positive breast cancer: A single-arm phase 2 trial (Brecan Trial).
Authors: Yang Jixin , Yang Yuqing , Wen Xinxin , Wu Jiang , Yu Jing , Wang Lei , Huang Meiling , Hu Wenyu , Ma Wen , Li Nanlin
Published: June 2022

e12622

Background: Despite that AC-THP regimen is one of the commonly used regimens for neoadjuvant treatment of HER2-positive breast cancer, previous studies showed that pCR rate rarely exceeds 70%. We hypothesized that prolonged dual anti-HER2 therapy can increase pCR rate in neoadjuvant therapy. In this study, we designed a single-arm trial of ACHP-THP regimen (continuous dual anti-HER2 therapy of trastuzumab and pertuzumab) in neoadjuvant therapy of HER2 positive breast cancer. To minimize adverse cardiovascular events, we used pegylated liposomal doxorubicin (PLD) and Nab-Paclitaxel (Nab-P) instead of doxorubicin and paclitaxel. We aimed to examine whether continuous dual anti-HER2 therapy can boost pCR rate in the neoadjuvant therapy. The cardiotoxicity was closely monitored when the anti-HER2 therapy was combined with PLD and Nab-P respectively. Methods: Upon approval by the Medical Ethics Committee of Xijing Hospital, patients with HER2-positive breast cancer (cT2-3/N0-1/M0) receiving neoadjuvant therapy, were enrolled. The patients were treated with PldCHP (pegylated liposomal doxorubicin 35mg/m2, cyclophosphamide 600mg/m2, trastuzumab 8 mg/kg loading, then 6 mg/kg, pertuzumab 840 mg loading, then 420 mg, iv, q3w) for 4 cycles followed by Nab-PHP (Nab-Paclitaxel 260mg/m2, trastuzumab 6 mg/kg, pertuzumab 420 mg, iv, q3w) for 4 cycles, with strict monitoring of cardiotoxicity. The primary endpoint was pCR rate, and secondary endpoint was cardiotoxicity during neoadjuvant therapy. Results: From January 2020 to October 2021, a total of 96 patients were recruited. Among the 96 patients with a median age of 49 (21-71), 58 patients were HR positive and 42 patients had positive lymph node status. Overall, the pCR rate was 80.2% (77/96). The ER-positive tumor achieved a higher pCR rate than ER-negative tumor (82.8% vs 76.3%, p=0.439), but the difference was statistically insignificant. Multivariate regression analysis showed that for participants older than 30, HER2 3+ (IHC) showed a statistically significant positive influence on pCR rate. The common adverse reactions of grade ≥3 were neutropenia (30.2%), asthenia (8.3%), and peripheral sensory neuropathy (7.3%). Left ventricular insufficiency was detected in 4 patients, and no cardiotoxic events higher than grade 2 occurred during the neoadjuvant therapy. There was no treatment-related death. Conclusions: The PldCHP---Nab-PHP regimen is a feasible and effective neoadjuvant therapy for early stage HER2-positive breast cancer, showing high pCR rate and acceptable cardiotoxicity. These results support a further random controlled trial testing for continuous dual anti-HER2 therapy combined with PLD in neoadjuvant or adjuvant therapy of HER2 positive breast cancer.
A novel patient-derived organoid model for triple-negative breast cancer patients with residual disease after neoadjuvant chemotherapy for screening personalized drugs.
Authors: Liu Feiyang , Ma Dandan , Liu Qingsong , Qi Xiaowei
Published: June 2022

e12625

Background: Triple-negative breast cancer (TNBC) patients with residual disease after neoadjuvant chemotherapy (NAC) have high risk of recurrence. In this study, we developed a novel organoid culture method for growing TNBC patient samples after NAC, with the goal of generating models that more faithfully recapitulates the key features of the primary tumor for screening personalized drugs. Methods: We established organoid lines derived from TNBC patients who had residual tumors after anthracycline and taxane±platinum based NAC as well as normal human mammary tissues. The histopathology signatures of organoid lines were characterized by H&E staining and immunohistochemistry. The genetic and transcriptional features of organoids were analyzed by targeted sequencing and RNA sequencing. A set of clinical drugs were screened for their ability to suppress cancer organoids in vitro and the consistency was also analyzed between clinical response and drug efficacy of organoid models. Results: A total of 10 cancer organoid lines were successfully established, and cultured stably for more than 4 months. For comparison, 2 organoids derived from normal mammary tissues were generated as well. Our success rate for establishing cancer organoids from TNBC patient samples after NAC was 83% (10 out of 12 samples), and for organoids from normal mammary tissues, it was 100% (2 out of 2 samples). These organoid lines closely recapitulated the histopathology, genetic and transcriptional signature, and intratumor heterogeneity of the primary tissues. We found that active PI3K/AKT/mTOR pathways signaling is always required for cancer organoids from TNBC patient samples after NAC, while Wnt pathway activation is dispensable for generation of them in comparison to the organoid cultures from normal breast tissues. More importantly, we found that the anti-Trop-2 antibody-drug conjugate sacituzumab govitecan (IMMU-132) showed higher sensitivity to most cancer organoids from TNBC patient samples after NAC (8 out of 10 samples) with IC50 ranging from 0.3 nM to 86 nM in contrast to 5-FU (5 out of 10 samples) with IC50 ranging from 0.9 μM to 10.2 μM in vitro, whose prodrug capetabine is considered as a standard option in the postneoadjuvant setting. These results were also confirmed in patient-derived tumor xenograft models. The consistency of drug efficacy in the established cancer organoids and the patient responses in the clinic reached to 70% (7 out of 10 samples). Conclusions: We established a novel organoid culture system for TNBC patient samples after NAC, which was potentially a useful platform to explore molecular characteristics of TNBC patients after NAC and discover personalized drugs for intensive treatment.
Immunological profile could be responsible of the unusual long-lasting cutaneous-only breast cancer recurrence: An observational study.
Authors: Rebollo Joseba , González-Manzano Ramón , Sureda Manuel , Martínez Elena Ma , Monedero Elena , Bretcha Pedro , Brugarolas Antonio
Published: June 2022

e13000

Background: A small number of breast cancer patients develops long-lasting loco-regional cutaneous recurrent disease with a delayed appearance of systemic disease. We recently have observed a favourable immunological signature in one patient and thereafter we looked back to the institutional series to formulate a possible hypothesis. Methods: Two datasets of resistant and metastatic solid tumors (362 Agilent microarrays and 169 RNA sequencing), have been studied. Three immunological signatures have been applied (T-cell inflamed, Cytolysis and TMM) and patients with at least one positive signature have been identified. Results: Preliminary evidence identified, from our genomic and transcriptomic advanced breast cancer database (73 patients and 80 procedures), three patients (4%) with loco-regional only cutaneous recurrent disease. Two patients (#1 and #2) were Hormone Receptor-negative, HER2 receptor-positive with a long-lasting breast cancer cutaneous recurrence (57 and 42 months, respectively) until bone (#1) or visceral (pleura and liver) (#2) progression. Patient #3 is a Hormone Receptor-positive, HER2-negative breast cancer that has recently developed an ipsilateral cutaneous (breast) recurrence so we do not have a follow up. Patient #1 had 4 transcriptomic tests, patient #2 had 2 tests and #3 one test. Biopsies were obtained from cutaneous lesions. According to our database, 25 out 80 procedures (31.25%) showed at least one favourable immunological signature (Table). In patients #1 and #2 with consecutive genomic testing, the immunological profile got worse with the resistance to therapies before systemic progression. Conclusions: According to our observation, a positive immunological signature was associated with a loco-regional cutaneous breast cancer recurrence and an unusually prolonged course of the disease. This observation should be confirmed in larger trials with more patients. Immunotherapy might play a role in the management of this clinical situation. None of these 3 patients had a triple negative phenotype for which immunotherapy has been found active. Ayers et al. J Clin Oncol 2017; 127 (8):2930-2940. Yang et al. Clin Cancer Res 2020; 26(8):3296-3306. Manzano et al. BMC Cancer 2021: 432.[Table: see text]
Palliative care among metastatic breast cancer patients in the end-of-life period in the U.S.
Authors: Subramaniam Divya S. , Zhang Zidong , Jenkins Alexandria , Hinyard Leslie J.
Published: June 2022

e13002

Background: Research has shown that palliative care improves the quality of end of life care, and lowers associated costs for cancer patients. The purpose of this study was to determine utilization of palliative care consult (PCC) on or after date of metastasis to date of death, the association of emergency department (ED), intensive care unit (ICU) and chemotherapies among metastatic breast cancer (MBC) patients in the United States. Methods: We conducted a retrospective study using the de-identified electronic medical record data from a national healthcare informatics provider and insurer between January 1, 2000 and December 31, 2018. The MBC patients (age ≥ 18 years) who were diagnosed with a secondary neoplasm after the index diagnosis of breast cancer and deceased in the period of data capture were included. The cohort was split into the PCC groups, patients who had received at least one PCC on or after the date of metastasis through date of death; and the non-PCC group. The ED, ICU and chemotherapy encounters since metastasis were defined by ICD-9/10, HCPCS or CPT codes per encounter records. We quantified the ED and ICU visits within two months of death; and the antineoplastic chemotherapies within one and two months of death. Time from metastasis to death and utilization of services were compared between the PCC and the non-PCC groups using Whitney U-test and Chi-squared test. Results: 979 deceased MBC patients had at least one PCC and 1,636 did not at all. Overall, average patient age at the last admission was 68.7+/-12.9 years. The median time from metastasis to death was 9 (2 – 24) years. More than half of them were Caucasian (79.8%) and nearly half from the Midwest region (47.1%). Between the two groups, age distribution was not significantly different, but the PCC patients were more likely to have shorter time to death (8 vs 10 years), be African American (12.8% vs 9.8%), reside in Midwest (52.9% vs 43.7%) and have experienced complications since metastasis except for acute cerebrovascular events. Compared to the non-PCC patients, the PCC patients were more likely to use ED (52.2% vs 22.2%), ICU (12.5% vs 13.4%) within two months of death, and to receive chemotherapy within one and two months of death (17.7% vs 13.9% and 12.9% vs 6.0%, respectively). Conclusions: Our study found that only 38% of BC patients received at least one PCC following date of metastatic diagnosis. Findings highlight the need to increase PCC among MBC patients immediately following diagnosis to ensure appropriate care is provided and utilized. Furthermore, educational and informational interventions will need to be developed to boost PCC utilization among MBC patients.
Cytokine as an potential prognostic factor associated with absolute value of neutrophil and serum albumin in breast cancer patients.
Authors: Zhu Ye , Zhang Jingyi , Chen Chong , Tong Zhongsheng , Zhao Weipeng
Published: June 2022

e13007

Background: Cytokines are involved in many inflammatory diseases through various ways and play an important role in tumor immune regulation. With the development of molecular biology these years, researchers have found that breast cancer is not only related to genetic and environmental factors, but also to the chronic inflammation and immunity. But at the moment，there are few studies on the prognostic evaluation of serum cytokines in breast cancer. The correlation between serum cytokines and leukocytes was not clear. The purpose of this study is to investigate the value of serum cytokines in prognosis of breast tumors and their relationship with leukocyte characters and serum albumin level. Methods: A total of 75 serum samples and clinicopathological data of breast cancer patients from Tianjin Medical University Cancer Institute and Hospital were collected. The expression levels of 12 cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, TNF-α, IFN-α, IFN-γ) in serum were detected by immunofluorescence method. The absolute value of different kinds of leukocyte were determined by automatic blood analyzer. The concentration of albumin (ALB) was determined by bromocresol green method (BCG method). Univariate Cox regression and multivariate Cox regression were used to analyze the influence of the above indexes and clinicopathological features on the prognosis of patients. The correlation between the expression of cytokines and the absolute value of various kinds of leukocyte and serum albumin was studied by using multiple regression analysis. Results: A multivariate Cox proportional risk model was established by including breast cancer stage, molecular typing, IL-10, IL-12p70, absolute value of neutrophil, serum albumin and dipeptide aminopeptidase. It showed that different breast cancer stage (HR=0.415, 95%CI 0.191-0.902, P=0.026), and IL-10 (HR=0.177, 95%CI 0.038-0.821, P=0.027) were independent prognostic factors, Luminal B breast cancer had a statistically significant impact on survival compared with triple negative breast cancer (HR=0.193, 95%CI 0.067-0.554, P=0.002). The effect of other variables on survival was not statistically significant (P>0.05). Multiple linear regression analysis model demonstrated that the absolute value of neutrophils (b=1.498, t =2.938, P=0.005) and serum albumin (b=1.253, t=2.777, P=0.007) had statistically significant differences on IL-10, but breast cancer stage (b=0.635, t=1.776, P=0.08) and dipeptide aminopeptidase had no significant difference (b=0.952, t=1.715, P=0.091). Conclusions: Serum IL-10 plays an important role in indicating the prognosis of patients with breast cancer and its expression level was closely correlated with absolute value of neutrophil and serum albumin.