bluuebunny/crossref_metadata_2025 huggingface dataset:
Lorlatinib for advanced ALK and ROS1+ non-small cell lung cancer (NSCLC): Efficacy and treatment sequences in the IFCT-1803 LORLATU expanded access program (EAP) cohort.
Authors: Baldacci Simon , Avrillon Virginie , Besse Benjamin , Mennecier Bertrand , Duruisseaux Michael , Mazieres Julien , Descourt Renaud , Doubre Helene , Dubray-Longeras Pascale , Cadranel Jacques , Moro-Sibilot Denis , Ricordel Charles , Galland-Girodet Sigolène , Monnet Isabelle , Otto Josiane , Schneider Sophie , Missy Pascale , Morin Franck , Westeel Virginie , Girard Nicolas
Published: May 2020

9615

Background: Lorlatinib, a third-generation tyrosine kinase inhibitor targeting ALK and ROS1, has been made available in France starting October 2015 through an EAP for advanced, refractory, ALK+ NSCLC after the failure of chemotherapy and TKIs. Besides the landmark, multi-cohort phase II trial that assessed lorlatinib in ALK+ NSCLC, real-life evidence regarding the efficacy and safety, as well as treatment sequences including lorlatinib, is lacking. Methods: We report the cohort of consecutive patients with advanced, refractory, ALK or ROS1+ NSCLC enrolled in the French EAP of lorlatinib from October 2015 to October 2019. Data were collected from medical records by French Cooperative Thoracic Intergroup (IFCT) research study assistants on site. Primary endpoint was progression-free survival. Results: 200 patients were included: 143 (71.5%) ALK+, 57 (28.5%) ROS1+, 87 (44%) men, 127 (66%) never-smokers, and 167 (85%) stage IV disease. Mean age was 59 years. At the time of initiation of lorlatinib, 146 (74%) patients had Central Nervous System (CNS) disease (78 % for ALK+, 63% for ROS1+), 131 (76%) were PS 0/1. Lorlatinib was delivered as 2nd/3rd/4th/5th+ line in 3%/17%/27%/53%of ALK+ patients and in 30%/30%/16%/24%of ROS1+ patients, respectively. 150 (75%), 185 (93%), 138 (69%), and 80 (40%) patients had received prior chemotherapy, crizotinib, 2nd generation TKIs, and brain radiotherapy, respectively. Median PFS and OS from the initiation of lorlatinib were 11.8 (95% CI 7.3-14.6) months and NR (95% CI 18.6-NR) months, respectively for ALK+ patients and 7.6 (95% CI 6.2-10.2) months and 20.9 (95% CI 10.0-NR) months, respectively for ROS1+ patients. ORR and DCR were 46.2% (95% CI 37.6-54.7) and 86.2% (95% CI 80.2-92.1), respectively for ALK+ patients and 47.1% (95% CI 33.4-60.8) and 88.2% (95% CI 79.4-97.1), respectively for ROS1+ patients. CNS ORR was 41.7% (95% CI 33.3-50.1) and 37.7% (95% CI 24.7-50.8), respectively. With a median follow-up of 15.6 (95% CI 14.0-17.6) months, progression under lorlatinib treatment was observed in 71 (50%) ALK+ patients and 35 (61%) ROS1+ patients, and CNS progression in 24 (34%) and 8 (23%) patients, respectively. The safety profile of lorlatinib was consistent with published data. Conclusions: These real-life results confirmed lorlatinib as a major treatment option for patients with advanced refractory ALK or ROS1+ NSCLC.
Breast cancer recurrence rate in patients treated for early breast cancer.
Authors: Munguti Cecilia , Mutebi Miriam Claire , Ng'ang'a Mukuhi , Wasike Ronald
Published: May 2020

e12508

Background: Recurrence rates for early breast cancer vary in different studies from 7% to 18%. Recurrent breast cancer is associated with poorer outcome and higher mortality rates. The recurrence rate in the Kenyan population remains unknown despite high prevalence of known risk factors. Methods: Single institution retrospective study of all women (18 -75 years) treated for early breast cancer at a single center private tertiary unit from 2009 to 2017. Results: 239 patient records were reviewed. The mean age at diagnosis was 51 (SD13.1). 98% of women presented with a palpable breast lesion. The molecular sub-type’s prevalence was: ER/PR+ (76%), triple negative (12.1%), HER2+ (2.9%). The overall recurrence rate was 7.2%, 66% recurrences were loco-regional, while 27% were metastatic disease, with 61% of the recurrences being detected initially on clinical/ self-breast examination. 77% of the recurrences were in women with ER/PR+ molecular sub-types. Recurrences in women with DCIS (2/27) were invasive breast cancers. There were no identified risk factors on uni-variate and multivariate regression analysis which conferred a risk of breast cancer recurrence. Discussion: The mean age at diagnosis in this group is younger than the western average (65 - 75 years). Majority of the women presented with symptoms – a presentation that differs from that of countries with a national breast cancer screening program. The molecular distribution of breast cancers is comparable to western populations. Conclusions: Recurrence rate for early breast cancer in this series is 7.2%, which is comparable with documented western data, with majority of the recurrences being detected initially on clinical/self-breast examination.
Efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor in the prevention of chemotherapy-induced neutropenia in patients with breast cancer.
Authors: Chong Xiaoyu , Zhu Xiaoli , Li Xuejuan , Gao Lingna , Ma Hongfang , Chong Baogui
Published: May 2020

e12515

Background: To explore the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF, brand name: Jinyouli) in the prevention of neutropenia in breast cancer patients receiving adjuvant chemotherapy with EC regimen (epirubicin combined with cyclophosphamide). Methods: Retrospective analysis was conducted on breast cancer patients receiving adjuvant chemotherapy with EC regimen in Hengshui People's Hospital between January 2018 to October 2019. In cycle 1, all patients developed grade 3/4 neutropenia and PEG-rhG-CSF was used prophylactically in the subsequent cycles. The incidence of grade 3/4 neutropenia, febrile neutropenia (FN), chemotherapy delay and dose adjustment were observed as well as relative dose intensity (RDI), antibiotics application and adverse events. Results: 96 breast cancer patients were enrolled and all of them developed grade 3/4 neutropenia (100%) in cycle 1. After secondary prophylactic use of PEG-rhG-CSF, the incidence of grade 3/4 neutropenia decreased to 26.32% (25/95), 12.50% (10/80) and 13.63% (9/66) in cycle 2-4, respectively, with a statistically significant difference with cycle 1 ( P<0.001); The incidence of FN decreased from 2.08% (2/96) in cycle 1 to 0% (0/95), 1.25% (1/80) and 0% (0/66) in the subsequent cycles ( P>0.05). The incidence of chemotherapy delay was 2.08% (2/96), 2.50% (2/80) and 1.52% (1/66) in cycle 2-4, respectively, and the incidence of dose adjustment was 9.38% (9/96) in cycle 2. There was no dose adjustment in cycle 3-4. The average RDI was 92%, 92% and 94% in cycle 2-4, respectively. The most common treatment-related adverse events were fever (2.08%), muscle pain (1.04%) and fatigue (1.04%). Conclusions: PEG-rhG-CSF secondary prevention can effectively reduce the incidence of neutropenia in breast cancer patients receiving adjuvant chemotherapy with EC regimen, which ensures the implementation of standard-dose chemotherapy with good safety.
The adjuvant radiotherapy benefits on pure mucinous breast carcinoma patients in different age stages: A SEER-based study.
Authors: Wei Xiaoqing , Dian Li ping , Tang Fan , Zhao Huijun , Situ Honglin , Xu Rui , Ren Liping , Zhang Yuzhu , Chen Qianjun
Published: May 2020

e12519

Background: The aim of this analysis is to study the prognostic impacts of adjuvant radiotherapy on pure mucinous breast carcinoma patients in different age stages. Methods: Patients diagnosed pure mucinous breast carcinoma between 1998 and 2015 were identified from the Serveillance,Epidemiology,and Results End database. Chi-square, Kaplan-Meier method, Multivariate Cox proportional hazards models were used for statistical analysis. Results: We enrolled 10656 patients, including 5758 (54.0%) and 4898 (46.0%) in the with radiotherapy and without radiotherapy cohorts, respectively.The K-M method shows age is an independent prognostic factor in pure mucinous breast carcinoma patients with radiotherapy( p= 0.000 ). Compared with the younger groups (<45y and 46-54y),the older groups (55-64y, 65-75y and >75y) show a greater benefits with radiotherapy. The multivariate Cox proportional hazards model shows significant difference (all p= 0.000), the group 55-64y((HR = 0.58, 95%CI:0.453–0.742),the group 65-75y(HR = 0.709, 95% CI: 0.610–0.825),the group>75y (HR = 0.613, 95% CI: 0.543–0.691), which indicates a better radiotherapy benefits in older groups(especially in 65-75y). Conclusions: This study shows a better benefits of postoperative adjuvant radiotherapy in pure mucinous breast carcinoma older patients. Owing to the common incompleteness of systematic basic treatments in older breast cancer patients,our real world analysis results may be helpful for the clinical decision-making.
Safety and clinical evaluation of dual inhibition with pertuzumab and trastuzumab in HER-2-positive breast cancer patients.
Authors: Suppan Christoph , Steiner Daniel , Klocker Valentina Eva , Posch Florian , Henzinger Elisabeth Christina , Stoeger Herbert , Dandachi Nadia , Balic Marija
Published: May 2020

e12520

Background: The addition of Herceptin to standard chemotherapy improved survival in patients with Her-2-positive breast cancer in neoadjuvant, adjuvant and metastatic setting. In higher tumor stage, the addition of pertuzumab is now standard of care and associated with a favorable toxicity profile. The purpose of this study was to evaluate the safety and efficacy of the biosimilar trastuzumab-dttb in combination with pertuzumab in Her-2-positive breast cancer patients. Methods: Thirty-five female patients with Her-2-positive breast cancer treated at the Division of Oncology at the Medical University of Graz between September 2018 and August 2019 were included. Summary measures are reported as medians 25th– 75thpercentile for continuous variables and as absolute frequencies (%) for count data. Results: Thirty-five patients received a median of four [3-7] cycles of trastuzumab-dttb plus pertuzumab. The median cumulative trastuzumab-dttb dose was 1904mg [1560-2640] and the median cumulative pertuzumab dose was 2100mg [1680-3360]. All patients had a normal baseline LVEF (> 50%) prior to the initiation of trastuzumab-dttb plus pertuzumab treatment with a median LVEF of 60% [60-65]. At completion of trastuzumab-dttb plus pertuzumab treatment (or in case of ongoing therapy the last EF assessment), the median LVEF was 60.0 % [58-62]. 21 patients had a median absolute LVEF decline of 1% -5-0], corresponding to a median percent change of 1.7 percent points [-7.7-0]. Two patients (5.7%) had a LVEF reduction ≤50%. None of the patients had a decline in LVEF of ≥ 10 %. In 8 patients, a switch from Herceptin to trastuzumab-dttb was tolerated well and these were also included in the analyses. In only two palliative patients, pertuzumab was either interrupted or stopped due to diarrhea and appetite loss, while trastuzumab-dttb was ongoing. 24 of 35 patients (69%) were treated with trastuzumab-dttb plus pertuzumab in the neoadjuvant setting. Two of these patients were treated for local relapse and were excluded for efficacy assessment. Of the remaining 22 patients, 11 patients achieved a pCR (ypT0/ypTis and ypN0). Conclusions: In these series of Her-2-positive breast cancer patients, the combination of trastuzumab-dttb/pertuzumab was consistent with the known safety and efficacy profile of Herceptin/pertuzumab.
Chemotherapy-induced neutropenia among breast cancer patients presenting to a tertiary hospital in Nigeria.
Authors: Salako Omolola , Okunade Kehinde Sharafadeen , Adeniji Adeoluwa Akeem , Fagbenro Gabriel , Afolaranmi Oluwasegun
Published: May 2020

e12523

Background: Neutropenia and febrile neutropenia are major dose-limiting adverse effects of systemic cancer chemotherapy. It has been associated with significant morbidity and mortality, and high costs of management, and treatment breaks in cancer patients especially in resource-limited environments leading to poorer outcomes. Chemotherapy-induced neutropenia is an established complication of breast cancer treatment, however, there is paucity of information on the exact magnitude of the condition. This study assessed the prevalence of neutropenia and febrile neutropenia, while identifying their associated factors. Methods: A cross-sectional study was conducted among 113 female chemotherapy-naïve breast cancer patients over a two-year period. Sociodemographic, clinical and haematological data was obtained via semi-structured interviews and from medical case files. Blood samples for complete blood count parameters were collected after each course of chemotherapy. The National Cancer Institute Common Terminology CTCAE version 4.03 was used to assess febrile neutropenia, neutropenia and its severity. Results: The prevalence of neutropenia and febrile neutropenia among the patients was 31.9% and 5.3% respectively. Throughout all courses of chemotherapy, there were neutropenic episodes 11.4% (57/502) with mild neutropenia 6.6%, moderate 3.4% and severe 1.4%. Prevalence of neutropenia decreased with increasing chemotherapy courses, with prevalence after first course being 14.2% and last course 4.9%. Associated risk factors for developing neutropenia include increasing age ( p = 0.014), ECOG performance score > 1 at presentation (p = 0.033) and presence of bone metastasis (p = 0.002). Conclusions: One in three breast cancer patients developed neutropenia while on chemotherapy. The use of prophylactic G-CSF after each course of chemotherapy should be a routine practice, especially among elderly patients, unstable patients, and those with bone metastasis.
High-risk of recurrence for nodal micrometastasis with breast pathologic complete response (ypT0/Tis ypN1mi) after neoadjuvant chemotherapy.
Authors: Garcia Torralba Esmeralda , de la Morena Pilar , Garcia Gomez Marina , Ivars Rubio Alejandra , Garcia Martinez Elena , Garcia-Garre Elisa , Martinez Galvez Maria , Zafra Gema Marin , Aguilar Jimenez Jose , Navarro Manzano Esther , Ayala Francisco
Published: May 2020

e12524

Background: Nodal micrometastatic disease (ypN1mic) after neoadjuvant chemotherapy (nCT) for breast cancer (BC) is considered an indication for axillary lymph node disection. While pN1mic prognostic impact has been extensively studied, the prognostic impact of ypN1mic disease is uncertain and these patients are usually grouped together with nodal macrometastatic disease. Since outcomes may be difficult to evaluate in the setting of BC residual disease, our aim was to compare the prognostic meaning of ypN1mic with that of ypN0 when a pCR is obtained in the breast. Methods: We retrospectively analyzed a series of 454 BC consecutive patients treated between 2010 and 2018 with neoadjuvant chemotherapy (nCT) based on anthracyclines and taxanes (plus antiHER2 treatment when appropriate). Pathologic complete response (pCR) was defined as ypT0/Tis ypN0. Patients with pre-nCT sentinel lymph node biopsy or without post-nCT pathologic evaluation were excluded. Disease free (DFS) and overall survival (OS) were analyzed with Kaplan-Meier curves and Cox regression models. Results: 454 BC patients were included, with 106 (24%) pCR. Median follow-up was 39 months. 99 (21.8%) patients obtained a pCR both in breast and axilla (ypT0/Tis ypN0), with 4 recurrences (4%) while only 7 (1.5%) patients had isolated nodal micrometastatic disease (ypT0/Tis ypN1mic), with 2 recurrences (28%). Median DFS was not reached for the ypN0 group and was 28 months (95%CI: 21.6-34.4 months) for the ypN1mic group (HR: 16.55, 95%cI: 2.68-102.37; p = 0.003). No differences were observed for OS (p = 0.77), although 2/2 ypN1mi showed distant recurrence (2/4 for ypN0 patients). Baseline clinical and pathologic characteristics were comparable between both groups, with no differences in performance status (p = 0.45), clinical nodal stage (p = 0.48), HER2 (p = 0.32), estrogen receptors (p = 0.93), grade (p = 0.34), presence of carcinoma in situ (0.60) or clinical complete response (p = 0.42). Clinical characteristics of patients with recurrence were also similar (100%: clinically positive nodes, negative estrogen receptors, no clinical complete response). Conclusions: Residual nodal micrometastatic disease after nCT seems to be associated with a higher risk of recurrence. Although longer follow-up and larger series are needed to confirm our data, these results support the escalation of post-nCT treatment even in patients with ypN1mic and breast pCR.
How much is too much? Multidisciplinary management of elderly early-stage breast cancer (BC) patients.
Authors: Berger Elizabeth R. , Veeravalli Srinivasa Sevilimedu , Morrow Monica , Heerdt Alexandra S.
Published: May 2020

e12525

Background: Optimal approach to early-stage breast cancer (BC) management in women ≥70y is unclear. Studies have demonstrated improved local control but no survival advantage with use of radiation therapy (RT) after breast-conservation therapy (BCT). The impact on survival of other management decisions, including breast procedure, axillary staging (AS), systemic treatment, and patient comorbidities is unknown. We evaluate the effect of each treatment decision on overall survival (OS), disease-free survival (DFS), and breast-cancer specific survival (BCSS). Methods: Patients age ≥70y with cT1N0/ER+/HER2- tumors undergoing surgery from 2011-2013 were identified from a prospectively maintained, single-institution database. Clinicopathologic features were evaluated. 10-year estimated mortality from comorbidity was calculated using a Suemoto index (SI). Univariate and multivariable associations were assessed using Cox modeling. Kaplan-Meier method was used to estimate OS and DFS. Results: 338 patients were identified: 312 (92%) underwent BCT; 26 (8%) had mastectomy. Median age was 75.5y (70-101); median tumor size was 1.0cm (0.1-1.9); median SI was 42.5(22-99). With a median follow-up of 60 mos, 25 patients died—1 from BC, for an OS rate of 92.8% and BCSS of 99.7%. 9 patients developed a locoregional recurrence and 1 developed distant recurrence, representing a 5-year DFS rate of 97.8%. There were no differences in DFS by age groups (≤75, 76-80, > 80; p = 0.1). On univariate analysis, DFS did not vary by age, breast procedure, or receipt of chemotherapy. It was improved in those who had AS and a lower SI (p < 0.01). OS was better in those patients who had AS, had recurrence score performed and had radiation therapy, reflecting lower SI. On multivariable analysis, lack of AS (HR 10.5, p < 0.01) and higher SI (HR 1.03, p < 0.01) were the only variables associated with worse OS. Lack of AS became non-significant in those > 80y. No treatment decision led to improved BCSS. When comparing patients with local or systemic recurrence vs those without recurrence, there was no difference in OS (p = 0.4) or BCSS (p = NS). Conclusions: Decisions in early-stage BC in the elderly are complex due to competing morbidities. While DFS and OS may vary based on treatment variables, no specific care component affected BCSS. Treatment discussions in elderly BC patients should emphasize the risks/benefits of each care component, taking into consideration the patient’s comorbidities and allowing for the patient’s understanding of outcomes and quality of life.
Analysis of the fatigue benefit, functionality, and body composition of a program of therapeutic exercise and healthy lifestyle habits in patients breast cancer operated.
Authors: Ruíz Sofía , Pajares Bella , Iglesias Campos Marcos , Roldán Jiménez Cristina , Cuesta Vargas Antonio , Alba Conejo Emilio
Published: May 2020

e12533

Background: Numerous studies support the benefit of physical exercise in breast cancer, with a lower rate of fatigue, lower risk of recurrence and greater survival. In addition, it prevents cardiovascular diseases, diabetes and obesity. The objective of this work is to analyze the effect of a program of physical exercise and habits of healthy life on fatigue, functionality and body composition in breast cancer patients of the Medical Oncology Unit of the Hospital Virgen de la Victoria, Malaga. Methods: Prospective study on 97 patients with breast cancer after completing locoregional treatment and systemic chemotherapy. Treatment with hormone therapy and trastuzumab was allowed. All patients were without disease, without cardiovascular history that contraindicated the program and have signed the relevant informed consent. The duration of the program was 3 months and the parameter measurement was performed before and after. The main objective was analyze cancer-related fatigue and secondary functional parameters, anthropometric and adherence to Mediterranean diet. Fatigue, parameters functional and adherence to Mediterranean diet were evaluated by tests specific and anthropometric by different measurements including use of Tanita TBF-300A. Results: 97 patients were recruited, with a median age of 52 years (32 and 69), 60% had received neo/adjuvant chemotherapy, 84% hormonal therapy and 12% trastuzumab. Most patients underwent conservative surgery. (76%). After 3 months of intervention, women improved significantly cancer-related fatigue (p = 0.000), levels of diet adherence Mediterranean (p = 0.000), as well as functional parameters. One was observed statistically significant improvement in limb functionality/mobility upper, lower limb and general functionality (p = 0.005, p = 0.013 and 0.000, respectively). No differences were observed in terms of mass index body, fat mass or lean mass. Conclusions: This study shows the benefit in functionality and fatigue of an exercise program therapeutic and healthy lifestyle habits in breast cancer operated patients. Despite a significant increase in adherence to the Mediterranean diet, it is not they observed differences in anthropometric parameters.
Adipophilin expression as an independent marker for poor prognosis of patients with triple-negative breast cancer.
Authors: Yoshikawa Katsuhiro , Ishida Mitsuaki , Yanai Hirotsugu , Tsuta Koji , Sekimoto Mitsugu , Sugie Tomoharu
Published: May 2020

e12552

Background: Adipophilin (ADP) is a lipid-regulating protein of the perilipin/adipophilin/tail interacting protein of 47 kDa (PAT) family that coats the surfaces of cytoplasmic lipid droplets. Lipids are essential for cellular proliferation in tumor cells, and ADP, which increases the efficiency of lipid use, may contribute to cancer growth. Some previous studies suggest that ADP expression can act as a prognostic marker for specific cancers. The aim of this study is to investigate the clinicopathological significance of ADP expression in patients with triple-negative breast cancer (TNBC). Methods: Using immunohistochemical staining and tissue microarrays, we analyzed the expression profiles of ADP, glutaminase, and glutamate dehydrogenase (key enzymes in glutamine metabolism) in 61 TNBC patients who underwent operation from January 2006–December 2018. Relapse-free survival (RFS) was compared based on ADP expression and the risk factors for RFS were analyzed. Results: Fourteen (23.0%) patients were ADP-positive. As compared to ADP-negative TNBC patients, ADP-positive TNBC patients correlated with poor RFS ( p = 0.032). Among the TNBC patients with high Ki-67 labeling index, those negative for ADP exhibited better RFS than those positive for ADP ( p = 0.049). Moreover, among the patients without adjuvant chemotherapy, those negative for ADP exhibited better RFS than those positive for ADP ( p = 0.080). ADP-positive patients correlated with a significantly higher recurrence based on multivariate analyses (hazard ratio, 4.89; 95% confidence interval, 1.04–23.0; p = 0.044). Moreover, ADP expression significantly correlated with the expression of glutaminase and glutaminate dehydrogenase ( p < 0.001 and p = 0.029, respectively). Conclusions: ADP expression is a novel marker for poor prognosis of patients with TNBC and might be superior to Ki-67 as a prognostic marker. ADP expression may be related to upregulation of glutamine metabolism in cancer cells of TNBC.
Biological analysis of HER2 equivocal (2+) cases in primary breast cancer.
Authors: Nishimura Reiki , Osako Tomofumi , Okumura Yasuhiro , Nakano Masahiro , Fujisue Mamiko , Arima Nobuyuki
Published: May 2020

e12555

Background: Overexpression and/or amplification of HER2 is observed in 15–20% of all invasive breast cancer cases. Breast cancer patients with HER2 overexpression can benefit from anti-HER2 therapy. HER2 IHC results are generally divided into four values (range, 0 to 3+). The cases with a HER2 (2+) value should be assessed using FISH. The aim of this retrospective study was to evaluate the biological variables and prognosis of HER2 (2+) cases according to the FISH status. Methods: Primary breast cancer patients (n = 5419) were enrolled in this study from January 2002 to September 2019. The factors investigated included nodal status, tumor size, nuclear grade, ER/PgR and HER2 status, p53 overexpression, and the Ki-67 index values. Positive for HER2 is categorized as having a HER2 value of 3 + or FISH amplified in equivocal cases. Results: The HER2 3+ rate in non-invasive carcinoma was higher than the rate in the invasive carcinoma cases (16.4% vs 12.9%; p < 0.0001). The distribution of HER2 IHC status in invasive carcinoma cases was 3+ (12.9%), 2+ (5.8%) and negative (84.3%). The FISH positive rate of the HER2 2+ cases was 57.0 % (158 cases). HER2 positivity significantly correlated with ER/PgR negative, p53 overexpression, higher Ki-67 value and nuclear grade. The FISH positivity of the HER2 2+ cases significantly correlated with PgR negative, p53 overexpression and higher grade. There were significant differences in biological variables between IHC 3+ and 2+/FISH positive, and between IHC 2+/FISH negative and IHC negative. Patients with HER2 3+ had significantly worse disease-free survival (DFS) rates than the cases before the approval of trastuzumab in Japan. However, there was no difference after trastuzumab was approved. Moreover, there was no difference in DFS according to the FISH status in HER2 2+ cases. Conclusions: HER2 positivity indicated a higher degree of malignancy. HER2 2+ had different independent biological characteristics from HER2 negative (0 & 1+) or positive (3+) cases. Therefore, the difference in biology of HER2 2+ cases may influence the prognosis and should be reconsidered in breast cancer cases.
The association between breast density and HER2-positive breast cancer: A population-based case-control study.
Authors: Tan Vivian , Payne Jennifer , Paquet Nicole , Iles Sian , Rayson Daniel , Barnes Penny , Abdolell Mohamed
Published: May 2020

e12556

Background: Little is known about the association between mammographic breast density and the subtypes of breast cancer including HER2-positive breast cancers (HER2-BrCa). The objective of this study was to assess the strength of association between breast density and HER2-BrCa in a population-based screening program. Methods: This is a population-based case-control breast cancer study of women aged 40 to 75 who underwent digital breast screening from 2009 to 2015 in Nova Scotia, Canada. Cases included women diagnosed with HER2-BrCa at screen or before their next screen (interval); controls included women without screen-detected cancer matched to cases by age and year of screen. Measures of mammographic breast density (percent density, BI-RADS-4th and -5th edition) were obtained from automated software (densitasai) and linked with clinical risk factor data (age, parity, total breast volume, post-menopausal status, hormone replacement therapy, family history and history of core biopsy). The association between breast density and cancer risk was assessed by calculating the odds ratios [OR] with 95% confidence intervals using multivariable logistic regression. Results: A total of 209 cases (median age, 58.8 years) and 6812 controls (median age, 59.4 years) were included. The risk of HER2-BrCa increased with increasing levels of percent breast density. High breast density according to BIRADS-4th and -5th editions was significantly associated with HER2-BrCa: BIRADS -4th 3/4 vs 1: OR 2.50 (1.68 - 3.68); BIRADS-5th C/D vs A: OR 2.58 (1.71 - 4.01). The association between higher breast density and increased risk of HER2-BrCa remained after adjustment for clinical factors. Conclusions: The risk of HER2-BrCa was associated with progressively higher mammographic breast density, although to a lesser extent than breast cancer in general. Accurate risk models including breast density may support the development of more breast-screening protocols that can lead to more strategic use of healthcare resources.
Immunogenicity and transcriptomic biology in Nottingham histologic grade 3 breast cancer.
Authors: Takahashi Hideo , Oshi Masanori , Asaoka Mariko , Yan Li , Takabe Kazuaki
Published: May 2020

e12563

Background: Cancer biology dictates disease progression and prognosis of a tumor. Histological grade has been used as a proxy of tumor biology in various cancer types, although it depends on morphological analysis of the tissue. As such, Nottingham histological grade is recently incorporated into the 8th edition of the AJCC Breast Cancer Staging. Herein, we hypothesized that Nottingham histological Grade3 breast cancer (BC) demonstrate strong immunogenicity in response to aggressive phenotypes, reflecting worse clinical outcomes. Methods: Clinicopathological data and transcriptomes were obtained from Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), The Cancer Genome Atlas (TCGA) Invasive breast carcinoma (BRCA) cohort, and GSE25066. While METABRIC was used as a training cohort, the other two cohorts served as validation cohorts. As TCGA did not contain pathological information, Nottingham histological grade was manually collected through the Text Information Extraction Systems (TIES). Results: 2876 patients were analyzed in this study. Grade1 tumors were 274 patients (9.5%), Grade2 tumors 1185 patients (41.2%), and Grade3 tumors 1417 patients (49.3%). Grade3 tumors were common in patients with Estrogen receptor (ER) negative (p < 0.001), with Her2 and Basal molecular subtypes by the PAM50 classifier (p < 0.001), and associated with increased MKI-67 expression (p < 0.001). Disease-free survival (DFS) was significantly worse in Grade3 tumors in all cohorts. Gene set enrichment analysis (GSEA) demonstrated that Grade3 tumors significantly enriched immune activity related gene sets as well as cell proliferation and cell cycle related gene sets. CIBERSORT also demonstrated that Grade3 BCs were infiltrated with anti-cancer macrophage M1, follicular helper T cells, and activated NK cells (all p < 0.001). Furthermore, Grade3 tumors were associated with more diverse T cell receptor (p = 0.001) and increased cytolytic activity (p < 0.001). Lastly, T cell exhaustion markers, including PD-L1, PD-1, and CTLA4, were significantly elevated in Grade3 BCs (all p < 0.001) as a negative feedback loop. Conclusions: Grade3 BCs demonstrated enhanced immunogenicity as well as aggressive transcriptomic features.
Correlation of hormonal receptor level and survival outcome in HER2-positive nonmetastatic breast cancer.
Authors: Chen Mengdi , Wu Jiayi , Zhu Li
Published: May 2020

e12568

Background: In human epidermal growth factor 2 (HER2)-positive breast cancer, emerging evidences imply that clinical behavior and prognosis differ according to hormone receptor (HR) status. However, there is no conclusion about the relevance between estrogen receptor (ER) or progesterone receptor (PR) expression and clinical outcome of HER2-positive breast cancer. Our study is designed to determine the effect of different ER/PR levels on survival benefit of HER2-positive early breast cancer. Methods: 984 non-metastatic HER2-positive breast cancer patients between January 2009 and December 2016 were retrospectively reviewed and HR+/HER2+ patients were further classified into several subgroups based on ER expression level (Low/L: 1-9%; Median/M: 10-74%; High/H: 75-100%) and PR expression level (Low/L: 0-19%; High/H: 20%-100%). Clinical features and survival outcomes were evaluated. Results: A total of 461 HR+/HER2+ and 523 HR-/HER2+ breast cancer patients were included in our study and 69.8% of them received target therapy (HR+ 67.5%, HR- 71.9%). While HR+/HER2+ breast cancer showed better survival than HR-/HER2+ subtype in 5-year disease free survival (DFS, 92.6% vs 87.6%, p = 0.002), no significant difference was observed between 5-year DFS rates in ER+/PR+ and ER+/PR- subgroup (94.3% vs 89.7%, p = 0.150). However, a possible correlation was found between ER/PR levels and DFS both in HR+/HER2+ (p = 0.057) and all HER2+ (p < 0.001) breast cancer. In HR+/HER2+ breast cancer, all subgroups showed DFS improvement trend versus M-ER/L-PR patients and hazard ratio of H-ER/H-PR subtype had a statistical difference (0.36, 95%CI 0.13-0.99, p = 0.047). In all HER2+ patients, hazard ratio of H-ER/H-PR compared with HR- subtype was 0.32 (95% CI, 0.13-0.80, p = 0.015). M-ER/L-PR presented similar DFS outcome with HR- subtype in our study. Conclusions: ER/PR expression may become a predictor of survival benefit in HER2-positive non-metastatic breast cancer and a higher ER/PR expression level might be associated with better DFS.
Survival outcomes of metaplastic breast carcinoma: An Indian tertiary care center data.
Authors: Puii Lalnun , Sarathy Vinu , Sangi Lalram , Thomas Beulah Elsa , Koramati Samuel Luke , Varayathu Hrishi , Mufti Suhail Sayeed , Mathew Smruthy Ann , Thungappa Satheesh Chiradoni , Naik Radheshyam , Ajaikumar Basavalinga Sadasivaiah
Published: May 2020

e12579

Background: Metaplastic breast carcinoma is a rare histological subtype that has basal like characteristics and is reported to have a poorer prognosis than no specific type/ductal carcinoma (ductal/NST). We aimed to investigate clinicopathological features and outcome from a single institution based registry. Methods: Clinical records of breast cancer patients treated during 2012-2019 were screened and 31 cases of metaplastic breast carcinoma were found. Descriptive analysis was done for patients’ demographics and clinicopathological features. Kaplan Meier method was used to assess survival outcomes. Results: The incidence of metaplastic breast cancer was 0.5% (31/6180) in our study out of which the most common histopathological differentiation was squamous (45.16%). The second most common was sarcomatoid histology (32.25%), followed by chondroid (9.68%) and mixed histology (12.9%). The median age at diagnosis was 60 years ranging from 28 to 82 years. 64.15% of patients were post-menopausal. At presentation, three (9.67%) patients had metastatic disease while the rest were diagnosed with early (51.61%) and locally advanced cancers (38.72%). Triple negative cancers (ER/PR/Her2 negative) constituted the vast majority with 22 cases (80.6%) while hormone receptor positive (ER/PR positive, Her-2 negative) and Her-2 neu positive (ER/PR negative) made up the rest with three patients (9.67%) each group respectively. The median overall survival was found to be 39 months (95% CI 25.46 - 52.53). Conclusions: After a thorough search in PubMed and Google Scholar, we could not find a larger case series from India with clinical outcomes for metaplastic breast carcinoma. Our results suggest that metaplastic breast carcinoma is a heterogenous disease. Outcomes of metaplastic breast carcinoma are relatively worse when compared with literature for triple negative breast cancer and breast cancer in general. Further biological understanding may offer valuable insights for newer targets and therapeutic approaches to metaplastic breast cancer.
Recurrence score (RS) differences between primary and second-primary breast cancer (BC): Exploratory analysis of the Clalit Health Services (CHS) registry.
Authors: Shachar Shlomit , Rizel Shulamith , Fried Georgeta , Leviov Michelle , Yerushalmi Rinat , Ben-Baruch Noa , Tokar Margarita , Soussan-Gutman Lior , Dvir Addie , Bareket-Samish Avital , Yablonski-Peretz Tamar , Sonnenblick Amir , Kaufman Bella , Hammerman Ariel , Liebermann Nicky , Stemmer Salomon M.
Published: May 2020

e12587

Background: In the phase 3 TAILORx study, the first invasive disease-free survival event (in all arms) was often opposite BC or other second primary cancer. Our goal was to investigate differences in the 21-gene RS results between the primary BC and a second primary BC, as well as the association with clinicopathological characteristics. Methods: This analysis of the prospectively-designed CHS registry included all CHS pts with estrogen receptor (ER)+ HER2-negative BC who underwent RS testing between 1/2006 and 6/2019 and for whom ≥2 RS results were identified which were > 1 year apart. Results: Of the 10,244 RS assays ordered in this time frame, 371 involved pts for whom the assay was performed at least twice. Our analysis focused on the 42 pts for whom the assays were performed > 1 year apart. All pts were females; 76% were initially diagnosed with node-negative BC; median (interquartile range [IQR]) age at first diagnosis was 56 (43-64) yrs. Tumor characteristics for the first and subsequent primary BC are presented (Table). The median time (IQR) between the first and latest RS assay was 4.5 (2.9-6.4) yrs. In 28 pts (67%), the latest primary BC was ipsilateral and in 14 (33%) it was contralateral. The median (IQR) difference between the first and latest RS value was 7 (1-12). The second/third primary BC had higher RS than the first BC in the majority (76%) of pts. Higher RS in the latest primary BC (compared to the first primary BC) was more common when the latest primary BC was ipsilateral than when it was contralateral (86% vs 57%, P= 0.04). Conclusions: In ER+ HER2-negative BC pts, second/third primary BC is generally associated with higher RS result (compared to the first primary BC), particularly if the later primary BC is ipsilateral. [Table: see text]
The association between race and intrinsic subtype on hormone receptor-positive breast cancer among young black women.
Authors: Reid Sonya , Moore Jaleesa , Tezak Ann , Weidner Anne , Mayer Ingrid A. , Pal Tuya
Published: May 2020

e12591

Background: Hormone receptor-positive, HER2-negative breast cancer (HR+/HER2- BC) has the highest incidence and mortality rate across all racial/ethnic groups. HR+/HER2- BC is clinically and biologically heterogenous. Gene expression profiling assays can provide prognostic information and predict risk of late recurrence among women with HR+/HER2- BC. Prior studies have shown worse clinical outcomes among black women with HR+/HER2- BC. We sought to compare the distribution of intrinsic subtypes among young black women with HR+/HER2- BC, compared to published data from a young white cohort in the Carolina Breast Cancer Study (CBCS). Methods: Two population-based cohorts of black women diagnosed with BC between 2002 to 2012 at or below age 50 years were analyzed. Participants were recruited from twelve Southeastern states. All participants were asked to complete release of medical records and tissue/tumor forms to verify clinical information and to obtain primary tumor samples for future analyses. We compared the distribution of intrinsic subtypes and associations to clinical characteristics as compared to white female counterparts using Pearson chi-squared test. Results: Of 569 black participants, 124 women had HR+/HER2- BC and tumor samples available for analysis. There were 66 Luminal A (53%), 35 Luminal B (28%), 19 Basal (15%), and 4 HER2-enriched (3%) tumors. Black women with non-Luminal A tumors were younger ( < 40) with larger tumors ( > 2cm) and had higher risk of recurrence (ROR-T) scores as compared to black women with Luminal A tumors (p = 0.065, 0.006, and < 0.001, respectively). Compared to young white women in the CBCS, black women in our study had a significantly higher percentage of non-Luminal HR+/HER2- BC (p = 0.037). Conclusions: Our results suggest that among young women with HR+/HER2- BC, black women have a higher proportion of non-Luminal tumors compared to their white counterparts. Non-Luminal HR+/HER2- tumors (i.e., basal and HER2-enriched) are more aggressive and may be less sensitive to endocrine therapy. These results suggest that overrepresentation of aggressive HR+/HER2- BC subtypes may contribute to the racial survival disparity observed among black women.
Validation of the Van Nuys Prognostic Index in 737 patients with ductal carcinoma in situ (DCIS) treated at Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
Authors: Kunkiel Michal , Niwinska Anna , Jagiello-Gruszfeld Agnieszka I. , Michalski Wojciech
Published: May 2020

e12603

Background: To assess the value of the Van Nuys Prognostic Index (VNPI) used in Maria Sklodowska-Curie National Research Institute of Oncology (MSCNRIO) to select the most adequate method of the treatment of DCIS patients. Methods: The database covered 737 subsequent DCIS patients treated in MSCNRIO in the years 1996 -2011. The results of the treatment with and without compliance with the VNPI index were compared. Results: In the group of 737 patients 66 (9%) failures were reported. There were 4 (0.5%) deaths due to DCIS progression. After 15 years of observation of patients treated in compliance with VNPI, the percentage of failures after local excision (4-6 VNPI points), breast conserving treatment (7-9 VNPI points) and mastectomy (10-12 VNPI points) was 29%, 21% and 9%, respectively. No differences in the overall survival was observed. In patients with 4-6 VNPI points the percentage of recurrences in the group treated in compliance with the VNPI (without radiotherapy) was 29% while in the group treated without compliance with the VNPI (with radiotherapy) - 2%. Conclusions: The Van Nuys prognostic index (VNPI) does not seem to be an ideal tool in patients with DCIS. It shows too high percentage of recurrences in the low risk group (VNPI of 4, 5 or 6 points), treated exclusively with a sparing surgery. Almost all patients after surgical excision should be irradiated.
Predictors of post-mastectomy radiation (PMRT) in node-negative breast cancer patients.
Authors: Sheriff Laura , Cordeiro Erin , Hardy Jacob , Roberts Amanda
Published: May 2020

e12608

Background: Post-mastectomy radiation (PMRT) reduces the risk of locoregional failure for women with an elevated risk of recurrence from breast cancer. Therefore, PMRT is often indicated for women with node positive breast cancer including those with only 1-3 nodes involved. The need for PMRT in node negative breast cancer patients is less established. The objective of our study was to review the predictors of PMRT in women with node-negative breast cancer and evaluate the overall recurrence rates. Methods: A retrospective chart review was completed. Women with node-negative breast cancer who underwent mastectomy and sentinel lymph node biopsy at a regional breast cancer center between January 1st,2011 and December 31st, 2017 were included. Patient and tumor characteristics, treatment details and recurrence data were recorded. The primary outcome was recommendation of PMRT. Univariate analysis was completed and then a multivariable logistic regression was completed to determine independent predictors for PMRT. Results: Overall, 235 women with node-negative breast cancer underwent mastectomy and sentinel lymph node biopsy during the study period. Forty-three (18.3%) patients were recommended to undergo PMRT, with 39 of the 43 patients completing the recommended treatment. PMRT was offered more often to younger women (p<0.001), women with multifocal/centric disease (p=0.002), large tumors (p<0.001), high grade tumors (p < 0.001), lymphovascular positive tumors (p=0.04) and estrogen-negative disease (p =0.017). On multivariable analysis, the odds of radiation recommendation were highest for patients with high grade disease (OR 5.81, 95%CI: 2.08 – 16.20) followed by multifocal/centric disease (OR 3.12, 95%CI: 1.26 – 7.70). There were no differences in overall recurrence between patients who underwent PMRT versus those who did not have PMRT (p = 0.31). Conclusions: A moderate percentage of node negative patients are offered PMRT. Independent predictors for recommendation of PMRT in node negative patients are: decreasing age, increasing tumor size, multifocal/centric disease and higher grade disease. Surgeons can use this information to counsel patients regarding the possible need for PMRT, especially in the setting of planned immediate reconstruction.
Patients over 65 with early breast cancer and preference for intraoperative radiation despite no survival benefit.
Authors: Tang Annie , Kelly Jason F. , Cureton Elizabeth , Shim Veronica
Published: May 2020

e12612

Background: Patients over 65 years of age with early-stage hormone receptor (HR)-positive breast cancer have many radiation treatment options based on the PRIME II and CALGB 9343. Our study aims to evaluate treatment preference of patients over 65 years of age when intraoperative radiation therapy (IORT) is offered. Methods: A retrospective chart review was conducted among patients over 65 years old diagnosed with early-stage HR-positive breast cancer during 2016-2019 in a single breast program in a large integrated healthcare system. At our institution, every breast cancer patient is reviewed at a weekly multi-disciplinary breast conference for IORT eligibility and tracked prospectively. All patients in this study met with breast surgeons and radiation oncologists prior to their locoregional treatment decisions. We identified patients who were offered IORT as an option. The tumor board discussion, treatment team recommendation, and the final patient decision for radiation were obtained from the chart review. Demographics including age, race, hormone therapy, and co-morbidities (Charlson Comorbidity Index) were collected. Logistic regression analysis was used to evaluate if any factors were associated with patients’ radiation treatment choice. Results: Among 225 patients who were over 65 with early endocrine responsive breast cancer, 63 patients met the IORT guideline (28%). Their ages ranged from 65-86 with a mean of 70.4 years. 74.6% of patients chose IORT compared with 14.3% who opted for whole breast radiation. Only 4.8% of patients chose to omit radiation after breast-conserving surgery, and 6.3% chose mastectomy. Patients who chose IORT was also more likely to take endocrine treatment (OR 4.76 CI 1.42-16.0, p = 0.01). Age, race, and co-morbidities were not associated with preference for IORT (OR 0.95 p = 0.34, OR 1.09 p 0.92, and OR 1.15 p = 0.53, respectively). Conclusions: Early-stage breast cancer patients over age 65 with HR-positive disease overwhelmingly desired radiation treatment even after being counseled that it does not confer an overall survival benefit. IORT was strongly preferred over whole breast radiation. This finding indicates that these women choose to maximize their local cancer control, regardless of its impact on overall survival, and prefer the convenience of single fraction, integrated radiation delivery. Further studies need to be completed on patient reported outcomes in this study population.