bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcome with pertuzumab, docetaxel, and trastuzumab (PTH) regimen in patients with HER2 positive metastatic breast cancer: Real-world data from a single center in India.
Authors: Gogia Ajay , Gupta Anshul , Batra Atul , Deo S.V.S , Sharma Daya Nand , Mathur Sandeep , Mishra Ashutosh , Prasad Chandra Prakash 
Published: June 2024

e13037 Background: Pertuzumab, Docetaxel and Trastuzumab (PTH) regimen constitutes one of the standard treatment regimens in human epidermal growth factor receptor-2 (HER2) positive metastatic breast cancer (MBC). The real-world outcomes of its use from the Indian sub-continent are lacking. Methods: We retrospectively reviewed the medical records of HER2-positive MBC treated with an upfront PTH regimen at the All India Institute of Medical Sciences, New Delhi, India, between Aug 2016 to July 2023. A total of six cycles of PTH [pertuzumab (840 mg loading followed by 420 mg), docetaxel (75 mg/m2), trastuzumab (8 mg/kg loading followed by 6 mg/kg) q21 days] were planned along with granulocyte-colony stimulating factor (GCSF) prophylaxis. Patients were continued on maintenance trastuzumab after 6 cycles (till disease progression) and hormonal agent if indicated. The primary outcome was progression-free survival (PFS). The secondary outcome was overall survival (OS), overall response rate (ORR) rates, and toxicity. Results: Eighty-seven were included with a median age of 48 years (range, 25-73). Overall, 38 (43.6%) patients had hormone-positive (estrogen receptor and or progesterone receptor) disease and 48 (55.17%) were premenopausal. Thirty-five (40.2%) patients had received prior adjuvant and neoadjuvant treatment. Eighty patients (91.5%) had visceral metastasis and the most common site was the liver followed by the lung. After a median follow-up of 36 months, the median PFS was 15 months and OS was 42 months. The ORR was 85.3% and complete response (CR) was observed in 14(16.09%) patients. The survival outcomes were significantly better among those with hormone-negative disease and among those who achieved CR after 6 cycles of PTH. Grade 3/4 toxicity was seen in 12% of patients which led to dose modification, interruption, and change in chemotherapy. Two patients developed reversible left asymptomatic ventricular systolic dysfunction. None of the patients developed congestive heart failure. The most common grade 3/4 toxicities were diarrhea in 8 (9.1%) patients, cutaneous rash in 2 (2.2%) patients and thrombocytopenia in 2 (2.2%) patients. There were two cases of febrile neutropenia. Conclusions: In a real-world context, PTH is an effective and well-tolerated regimen for in patients with HER2-positive MBC in India. Hormone-positive disease has poor survival compared with hormone negative disease.
Employing semi-quantitative methods to classify breast cancer markers (ER, PR, HER2, Ki67) expression, using the RT-qPCR based APIS Breast Cancer Subtyping Kit.
Authors: Gasior Anna , Wegscheider Anne-Sophie , Paveley Jack , Howard Kimberly Jane , Harrison Mathew , Gough Leanne , Gorniak Joanna , Rollinson Sara , Pounce Zoe , Niendorf Axel 
Published: June 2024

e13091 Background: Accurate determination of breast cancer (BC) biomarker status is crucial for guiding patient management decisions. Histopathologists commonly use semi-quantitative scoring systems to convert subjective observations of immunohistochemistry (IHC) marker expression into quantitative data, allowing a more detailed categorisation of marker status. The APIS Breast Cancer Subtyping Kit (BCSK) is an in vitro diagnostic test, detecting the relative expression of seven mRNA target genes ( ESR1, PGR, ERBB2, MKI67, CCNA2, PCNA, and KIF23) from invasive BC tissue. The APIS BCSK reports a positive/negative result for each biomarker alongside a molecular classification. Here, we demonstrate that by implementing additional RNA expression cut-off values, it is possible to generate a semi-quantitative result by further stratifying target expression into negative, low, medium, and high status using the APIS BCSK. Methods: 368 formalin-fixed paraffin-embedded (FFPE) samples of BC cases were used, obtained by core needle biopsy or resection. IHC scores were correlated with copy numbers as determined by an independently validated digital PCR (dPCR) assay and were used to set copy number cut-off values corresponding to IHC classification. The generated dPCR cut-off values were used to evaluate the corresponding ∆Ct values (RNA expression results derived from the APIS BCSK). For each target, three ΔCt cut-offs were established, facilitating classification into negative, low, medium, and high expression. Results: The semi-quantitative approach successfully classified target expression levels ( ESR1, PGR, ERBB2, MKI67). Overlap in ΔCt values was observed in central IHC categories for all targets, likely due to tumor heterogeneity and differing measurement methods for IHC and RT-qPCR. Despite these discrepancies, the derived cut-off values define a semi-quantitative scale for each target (Table). Conclusions: This study has established a methodology that utilises target copy number values and IHC protein quantification to establish ΔCt cut-off points. For each target we have defined four distinct groups as negative, low, medium, and high expression. This approach provides a semi-quantitative scale for evaluating each target with the APIS BCSK and serves as a valuable tool for classifying and understanding target expression levels. [Table: see text]
Efficacy and safety of abemaciclib in combination with endocrine therapy for HR+/HER2- advanced or metastatic breast cancer: A systematic review and meta-analysis.
Authors: Altaf Faryal , Qureshi Zaheer , Jamil Abdur , Siddique Rimsha , Fatima Eeshal 
Published: June 2024

e13096 Background: Breast cancer, particularly the HR+/HER2- subtype, remains a major global health concern. Abemaciclib, a CDK4/6 inhibitor, has shown promise in treating advanced cases. This study comprehensively assesses the efficacy and safety of Abemaciclib in combination with endocrine therapy for HR+/HER2- advanced or metastatic breast cancer. Methods: Following PRISMA guidelines, a systematic review and meta-analysis were conducted. A thorough literature search spanning PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov identified 22 studies. Inclusion criteria encompassed RCTs and retrospective cohort studies reporting on Abemaciclib in approved doses, either as monotherapy or in combination. Outcome assessments included PFS, ORR, SE/AE, and OS. Quality assessment utilized ROB II and NOS tools. Results: Analysis of 22 studies involving 14,010 patients revealed that Abemaciclib significantly improved PFS and ORR, with a 47% and 46% reduction in risk, respectively. A noteworthy 24% reduction in the risk of death was observed in the Fulvestrant combination group. However, Abemaciclib increased the risk of SE/AE by 104% and 304% in the Fulvestrant and NSAI combinations, respectively. Conclusions: Abemaciclib, particularly in combination with Fulvestrant, emerges as an effective therapeutic option for HR+/HER2- advanced or metastatic breast cancer, improving PFS and OS. The higher toxicity profile warrants cautious use, especially in treatment-naïve patients. This review informs future research directions and offers insights for clinical decision-making in the evolving landscape of breast cancer treatment.
Feasibility and tolerability of eribulin-based chemotherapy versus other chemotherapy regimens for patients with metastatic triple-negative breast cancer: A single-centre retrospective study.
Authors: Wang Lili , Huang Weiwei , Wang Chenxi , Chen Qi , Shen Yangkun , Huang Zhijian , Liu Jian , Lin Xiaoyan , Wu Fan , Chen Xinhua , Li Nani , Hong Yi , Chen Mulan , Li Jieyu , Huang Chuanzhong , Yu Suhong 
Published: June 2024

e13135 Background: Patients with Triple-negative breast cancer (TNBC) face a poor prognosis and limited therapeutic options. Current data on eribulin usage to treat TNBC is scarce. Therefore, we sought to compare the feasibility and tolerability of eribulin-based regimens with other chemotherapy regimens in patients with TNBC. Methods: This retrospective study was conducted at Fujian Medical University Cancer Hospital and included 159 patients with TNBC enrolled between October 2011 and January 2023. Patients underwent treatment with eribulin-based and other chemotherapy regimens. The study's primary endpoints were progression-free survival (PFS) and overall survival (OS), while its secondary endpoint was objective response rate (ORR), disease control rate (DCR), and safety. Tumour response was assessed using RECIST V.1.1 criteria. Results: Of the 159 participants in the study, 42 individuals (26.4%) received treatment with eribulin, whereas 117 participants (73.6%) were administered alternative chemotherapy regimens, which included nab-paclitaxel-based therapy (n=45) and platinum-based therapy (n=51). The follow-up period for all patients ended on December 31st, 2022, and the median follow-up time was 18.3 months (range:0.7-27.5). Following propensity score matching (PSM), eribulin-based treatment resulted in longer median PFS compared to platinum-based (hazard ratio (HR)=0.41, p=0.006), nab-paclitaxel-based (HR=0.36, p=0.001) and other chemotherapy (HR=0.39, p<0.001). Also, eribulin induced a remarkable prolongation of the median OS duration in all three comparative groups. The group receiving eribulin treatment showed significantly reduced incidences of any grade of anaemia, peripheral neuropathy, nausea and vomiting, and hair loss compared to other chemotherapy groups. Conclusions: For the salvage treatment of advanced TNBC, treatment with eribulin produced longer median PFS and OS than other chemotherapy regimens, with a well-tolerated safety profile. Therefore, further investigation of eribulin-based treatment in larger randomized trials for patients with advanced TNBC is warranted. Clinical trial information: NCT05953909 .
Treatment patterns of adenoid cystic carcinoma of the breast: A systematic review.
Authors: Macias Jonathan , Sales Nogueira Amorim Canedo Felipe , Lu Shou-En , Chen Chunxia , Heleno Caio Teixeira , Bridgeman Matthew , Goncalves Priscila Hermont , George Mridula Annette 
Published: June 2024

e13147 Background: Adenoid cystic carcinoma of breast (ACC-B) is a rare subtype of breast cancer (BC) accounting for 0.1% of all BCs. It shares histologic features with ACCs arising in the salivary glands and other locations. Given the hormone receptor (HR) negative phenotype [negative expression of the estrogen receptor (ER), progesterone receptor (PR)], some clinicians treat ACC-B as a basal subtype of BC, which is predominantly treated with chemotherapy. However, ACC-B has a more indolent and favorable clinical behavior. There are no established treatment guidelines for ACC-B. We conducted a systematic review of the literature on the treatment patterns for ACC-B. Methods: We followed the PRISMA criteria using the database in Cochrane, Embase, PubMed, Scopus, and Web of Science. The Covidence software was used for screening and data extraction. Eligible studies discussed the management of stage I-III ACC-B from 1960 to 2022. Individual patient (pt) demographics, tumor characteristics, treatment and outcomes were collected, when available. Results: The database search found 2864 studies, of which 187 articles met the inclusion criteria in the study protocol. Given the rarity of this subtype of BC, most studies were case reports (n=104). A total of 4370 pts with a median age of 57 years were eligible for analysis. Information on ER, PR and HER2 status was not available for all cases. For the cases in which this was reported, most were ER and/or PR negative (76% ER negative and 83% PR negative). Surgery was the primary treatment reported for 3984 pts. A total of 21.5% underwent mastectomy, 40.7% lumpectomy and 37.7% were treated with other modalities of surgery. In the group of patients for which information was available regarding the receipt of systemic therapy (n=3147), 82% did not receive neoadjuvant or adjuvant chemotherapy. Metastatic disease was reported to have developed in 2.2% of the total patients (n=98). Median time to recurrence was 31 months (0-460) with a median overall survival of 134 months (1-462). The most common site of metastases were the lungs (60%). Among the patients who developed metastatic disease and for whom initial treatment information was available; radiation was given to 32 pts, 26 received adjuvant chemotherapy and 15 received both radiation and chemotherapy. No patients that developed metastatic disease received neoadjuvant chemotherapy. Conclusions: Our results suggests that ACC-B has a clinical behavior different from basal subtype of BC. In our review, only 2.2% of pts relapsed with metastatic disease, even though most of the pts did not receive prior systemic therapy. We need to better understand the genomic landscape of ACC-B, to identify pts who may be at risk for recurrence and develop specific guidelines to treat this rare type of BC.
The long noncoding RNA MANCR to promote and stabilize triple negative breast cancer.
Authors: Warren Janine , Banerjee Bodhisattwa , Stein Janet , Stein Gary , Lian Jane 
Published: June 2024

e13150 Background: Cancer remains a leading cause of death worldwide, despite many advances in cancer treatment over the past decade. Triple Negative Breast Cancer (TNBC) is among the highest with a poor prognosis. Early diagnosis and modern treatment regimens for breast cancer (BC) have led to a high disease-free survival rate. Still, survival decreases significantly for patients with metastatic disease. Long non-coding RNAs are among a recent class of epigenetic regulators that function in the nucleus to support the stability of the cells and maintain the fidelity of chromatin interactions. Our laboratory discovered the long noncoding RNA MANCR (LINC00704) as being upregulated in human BC tumors and this is indicative of a worse survival rate than in patients with low MANCR-expressing tumors. MANCR is aberrantly expressed in TNBC cells, and these cells are highly dependent on MANCR to retain their tumorigenic characteristics. Methods: Our functional in vitro studies in MDA-MB-231 TNBC cells used GapmerRs to knockdown MANCR. For in vivo studies, TNBC cells were injected into the 4th mammary fat pad of mice, allowed initial tumor formation, and then treated the animals with 2 nmol/g of a negative control or MANCR targeting GapmeR. We also identified genome interaction sites at single nucleotide resolution by chromatin isolation by RNA purification (ChIRP)-seq to determine the mechanism of MANCR activity in TNBC cells. Results: We found that MANCR knockdown promotes DNA damage and decreases cell proliferation, migration, anchorage-independent colony formation, transwell invasion, and overall survival. Additionally, targeting MANCR in animals with existing tumors drastically inhibited tumor growth and the end-point tumor mass over time. The MANCR GapmeR treatment also inhibited the ability of TNBC cells to circulate and disseminate to distant organs. After performing ChIRP-seq in the MDA-MB-231 cells, we identified 988 genome-wide binding sites that exhibit MANCR interactions, of which 79% are intergenic and 21% are genic regions. Furthermore, 127 MANCR ChIRP peaks were found to overlap with fragile sites in the genome, indicating MANCR provides stability to these sites. Conclusions: These data suggest that targeting MANCR has therapeutic potential for patients with “MANCR-high” TNBC tumors by disrupting genome stability. Indeed, our in vivo studies demonstrate that “MANCR-high” TNBC tumors require MANCR to rapidly grow and promote disease progression. Lastly, many of the MANCR-chromatin interactions identified were found in intergenic regions and overlap with fragile sites within the genome. Collectively these data strongly indicate that MANCR stabilizes the TNBC genome, and disrupting genome stability by targeting MANCR has therapeutic potential.
Novel prognostic staging system for patients with de novo metastatic breast cancer: A real-world experience.
Authors: Khamees Ibrahim , Mahadevia Himil , Gosch Kensey , Sharma Parth , Chandra Simran , Gast Kelly C. , Pluard Timothy J. , Hensing Whitney L. 
Published: June 2024

e13167 Background: De novo metastatic breast cancer (dnMBC) is a heterogenous disease with variable survival rates. For newly diagnosed, non-MBC, the AJCC staging system incorporates non-anatomical factors, biomarkers and grade, in addition to tumor size and nodal status to define the prognostic stage group. These variables and other disease-related factors, such as sites of metastasis, have been associated with survival in MBC. Despite this, the current staging system groups all patients with dnMBC into a single prognostic group. More tools are needed to help clinicians relay important prognostic information to patients with dnMBC. Plichta et al. [1] utilized large population data sets to develop a novel staging system for dnMBC, which successfully stratified patients into four prognostic groups (IVA-D) based on disease-related variables. In this study, we sought to validate this staging system in an independent, real-world cohort of patients with dnMBC. Methods: We used a retrospective cohort of patients with MBC who received treatment in the Koontz Center for Advanced Breast Cancer (KABCC) at St. Luke’s Cancer Institute, a community-based healthcare system in the Kansas City metro area. The KABCC is a multidisciplinary clinic dedicated solely to the care of patients with MBC. Patients with dnMBC were assigned prognostic stage IVA, IVB, IVC, and IVD according to the system developed by Plichta et al. [1]. Overall survival (OS) was compared between groups using Kaplan-Meier analysis and the log-rank test. We also performed a stratified analysis based on age at diagnosis, <60 years versus ≥60 years. Results: Ninety-seven patients with dnMBC were included in the analytic cohort. Mean age at diagnosis was 60 years, and most patients self-identified as non-Hispanic White (71.1%) or Black (22.7%). Nine patients were assigned stage IVA (9.3%), 39 stage IVB (40.2%), 32 stage IVC (33%) and 16 stage IVD (16.5%). Most stage IVA were HER2 positive (66.7%), while most stage IVD were triple-negative (56.3%). OS differed significantly between the four stage groups, with mortality rates increasing as stage increased. This was true in both the overall population (p<0.001) and when patients were stratified by age at diagnosis (both p<0.05) (Table). Conclusions: In an independent, real-world cohort of patients with dnMBC, a novel prognostic staging system that incorporates biomarkers, T-stage, grade, and sites of metastasis successfully stratified patients into four prognostic groups. Our findings help to confirm the utility of this staging system in dnMBC. [Table: see text]
Preclinical analysis of the efficacy of near-infrared photoimmunotherapy and anti-PD-1 antibody combination therapy for treating CD73-positive lung cancer.
Authors: Chiba Ryohei , Nakajima Kohei , Hatanaka Kanako C , Ujiie Hideki , Aragaki Masato , Kobayashi Takuma , Konishi Teppei , Kinoshita Ichiro , Hatanaka Yutaka , Ogawa Mikako , Kato Tatsuya 
Published: June 2024

e14521 Background: The CD73/adenosine pathway, which converts extracellular ATP to adenosine, is emerging as a promising target for immunotherapy in various cancers. In the tumor microenvironment, hypoxia triggers upregulation of adenosine-activating molecules, including CD73, a membrane-anchored enzyme expressed on cancer cells. CD73 induces the expression of PD-1 and CTLA4, and all of this leads to immunosuppression. Therefore, we focused utilizing near-infrared photoimmunotherapy (NIR-PIT) to kill CD73-expressing cells and alleviate immunosuppression. NIR-PIT is an innovative cancer treatment approach which involves irradiating NIR light after the administrated antibody-photosensitizer conjugate binds to the target cells. Methods: In vitro, anti-CD73 antibody-IR700 conjugate was prepared and added to the CMT167 and LLC cell lines, which were irradiated with NIR light under a microscope. In vivo, a mouse model was established using the CMT167 cell line. The mice were divided into 6 groups: 1) NIR-PIT group against CD73; 2) anti-PD-1 antibody group; 3) combined treatment group of 1) and 2); 4) control group; 5) anti-CD73 antibody-IR700 conjugate group; and 6) near-infrared light irradiation group. Tumor volume and survival rate were compared among these groups. Additionally, after 2 weeks of treatment, tumors in the four groups 1) to 4) above were pathologically evaluated using two different AI-equipped software programs. Results: Microscope observation revealed that NIR-PIT induced immunogenic cell death of CD73-positive mouse lung cancer cell lines in vitro. In vivo, the effect of NIR-PIT on this mouse model was also demonstrated. Although previous studies have shown the efficacy of treatment with anti-CD73 antibodies, the present study compared the CD73-IR700 conjugate group to the NIR-PIT to CD73 group, and the latter group showed better therapeutic outcomes. Additionally, the combined treatment group displayed the highest anti-tumor efficacy in terms of survival and tumor volume. Pathological evaluation of the tumor interior showed a significant increase in tumor-infiltrating lymphocytes compared to the other groups. Additionally, the percentage of tumor cells was significantly reduced, while the percentage of stroma, including fibrous tissue, was significantly increased. In line with other studies that have already reported the additive effect of combination therapy with anti-CD73 antibodies and immune checkpoint inhibitors, the present study showed that the combination therapy resulted in further activation of immune cells and enhanced the therapeutic effect. Conclusions: CD73 represents a promising target for NIR-PIT, with potential for enhanced effectiveness when used in combination with immune checkpoint inhibitors.