bluuebunny/crossref_metadata_2025 huggingface dataset:
Relation between dexamethasone (DEX) usage, preventive trimetprim/sulfametoxazole (ST), and pneumocystis pneumonia (PCP) for patients with breast cancer receiving dose-dense AC followed by dose-dense paclitaxel (ddAC-ddP): Preplanned analysis of WJOG9016B.
Authors: Matsumoto Koji , Nishimura Meiko , Ozaki Yukinori , Futamura Manabu , Miyaki Toshikio , Tsurutani Junji , Imoto Shigeru , Doi Mihoko , Tokunaga Shinya , Aogi Kenjiro , Yoshimura Kenichi , Okada Hideaki , Sagara Yasuaki , Baba Motoi , Nagai Shigenori E. , Takano Toshimi ,   West Japan Oncology Group
Published: May 2019

e12022

Background: PCP is rare complication of ddAC-ddP. DEX is plausible risk factor for PCP. Dose and duration of DEX against CINV is changing over time as other anti-emetic drugs (5HT3 RA, NK1 RA, and olanzapin) became available. Then DEX usage varies widely in each hospitals. ASCO/IDSA guideline recommends preventive ST for patients receiving 20 mg or more predonisone equivalents daily for more than one month, although evidence is lacking in patients receiving ddAC-ddP. This study is to investigate relation between DEX usage, preventive ST, and risk of PCP for patients receiving ddAC-ddP. Methods: This study is preplanned analysis of WJOG9016B (UMIN000024992) which investigated relative dose intensity of ddAC-ddP supported by 3.6 mg (approved dose in Japan) of pegfilgrastim. Eligible pts were HER2 negative PBC with stage I to IIIc, going to start ddAC-ddP and younger than 65 y.o.. DEX usage and preventive ST usage were discrete to treating physicians. Results: From Jan. 2017 to Jan. 2018, 92 pts were registered and 91 pts were in the FAS set, because one patients turned out be ineligible after registration. All patients received DEX for prevention of delayed CINV. Median total dose of DEX during ddAC was 112 mg (range; 80 to 212 mg), which was equal to 13.3 mg (9.52 mg–24.76 mg) predonisone equivalents daily. Only five of them (5.4%) received more than 20 mg predonisone equivalents daily. Twenty patients received preventive ST. Three patients developed PCP. None of them with preventive ST developed PCP (0%), whereas three of patients without ST developed PCP (4.2%). These three patients received total DEX dose during ddAC at 80 mg, 112 mg, and 112 mg, respectively. Conclusions: ST was highly effective for PCP prevention for patients receiving ddAC-ddP, if DEX used against delayed CINV. Without ST prevention, the risk of PCP was 4.2 %, which was higher than threshold (3.5%) proposed in ASCO/ IDSA guidelines. The threshold of steroid dose leading to the risk of PCP might be lower than 20 mg or more predonisone equivalents daily in patients receiving ddAC-ddP. Clinical trial information: UMIN000024992.
Evaluation of androgen receptor expression in core needle biopsies and clinico-pathological factors in primary breast cancer.
Authors: Arima Nobuyuki , Nishimura Reiki , Osako Tomofumi , Okumura Yasuhiro , Nakano Masahiro , Fujisue Mamiko
Published: May 2019

e12023

Background: Immunohistochemistry (IHC) is used to determine breast cancer subtypes and to evaluate the ER, PgR, and HER2 expressions and the Ki-67 index value. The androgen receptor (AR) is frequently expressed in breast cancer but has not been standardized. IHC is recommended when using preoperative biopsy specimens to determine biomarker expressions. In this study, the differences in AR expression between core needle biopsy and matched surgical samples were investigated. The AR expression was evaluated as a predictor for neoadjuvant chemotherapy and grade of malignancy. Methods: Primary breast cancer patients (n = 363) who underwent surgery between March 2017 and December 2018 were divided into 3 groups; the core needle biopsy and matched surgical comparison group (n = 167), the neoadjuvant chemotherapy group (n = 54), and the without neoadjuvant chemotherapy group (n = 309). The AR expression was evaluated using IHC and the expression was divided into the negative, low ( < 10%) and high (≥10%) groups. Breast cancer subtypes were categorized using the IHC data derived from ER/PgR, HER2 and Ki-67 (cutoff 20%) values. Results: 1. There was no difference between the ER, PgR and HER2 expressions in the comparison group. AR was significantly lower in the surgical specimens. 2. The pCR rate was significantly higher in the ER and PgR negative cases. AR and the Ki-67 value did not correlate with pCR. 3. The AR positive rate was 61.2% in invasive carcinoma cases. Apocrine carcinoma showed a 100% positive rate. 4. AR expression significantly correlated with positive ER and PgR, a lower Ki-67 value, negative p53, and a lower nuclear grade. Luminal A type showed a higher AR rate (78.2%) than the TN and HER2 types. The AR rate was significantly lower (17.1%) in the TN type cases. Conclusions: discordance in the AR expression between the core needle biopsies and matched surgical specimens was found. AR expression using IHC should be evaluated in core needle biopsies.
Assessing adherence to hormone therapy (HT) in breast cancer (BC) patients receiving care at BC unit in a Uruguayan university of Hospital de Clínicas.
Authors: Castillo Cecilia , Camejo Natalia , Artagaveytia Nora , Hernandez Ana laura , Apud Patricia , Melo Florencia , Delgado Lucia Beatriz
Published: May 2019

e12026

Background: Adjuvant HT in Hormone Receptors (HR) + BC increases overall survival (OS). Adherence to therapy is a complex and multifaceted issue that can alter outcomes; however, not much of it is known abouth this in routine clinical practice. Methods: This was a retrospective study that enrolled patients treated with HT because of HR+ BC (stages I-III) at the BC unit in the 2002-2012 period. Methods: The proportion remaining on endocrine therapy was analysed by Kaplan-Meier curve. Univariate analysis (log rank test) was used to identify the factors that might independently impact on such discontinuation. The study was approved by the Ethics Committee of the Hospital de Clínicas. Results: 139 (73.1%) of the 190 patients enrolled were postmenopausal; their median age being 61 years. Most patients were single or divorced or widowed (121, 63.7%) and resided in the capital (125, 65.7%). Most tumors (166, 87.3%) were ductal carcinomas and most presented at a low histological grade: HG 2-3: 112 (58.9%). The distribution by stage was: SI: 63 (33.1%); SII: 82 (43.1%); SIII 39 (20.5%); S0 6 (3.1%). At the end of their first, second, third, fourth and fifth years of treatment; 95.3%, 87.9%, 80.6%, 76.4% and 69.5% of the patients still adhered, respectively. Adherence was not associated with either age (p = 0.687), menopausal status (p = 0.449), marital status (p = 0.221), origin (p = 0.5640), or stage (p = 0.168). The patients who received combined HT (tamoxifen followed by AI) adhered better than those who received one drug alone (p = 0.017). Conclusions: we assessed the adherence to HT in real life and found that it was reduced by 30.5% in 5 years, despite patients were well informed about the well-known benefit in terms of OS, of being a well-tolerated treatment and of being provided for free. These results are similar to or even better than those reported in several international studies. Further investigation is needed to understand why patients interrupt HT. We need to work harder to increase compliance, given the potential impact this may have on the patients’ OS.
Vitamin D insufficiency and risk of paclitaxel-induced peripheral neuropathy.
Authors: Jennaro Theodore Salvatore , Smith Ellen M. Lavoie , Vangipuram Kiran , Kidwell Kelley M. , Burness Monika Leigh , Griggs Jennifer J. , Van Poznak Catherine H. , Hayes Daniel F. , Henry Norah Lynn , Hertz Daniel Louis
Published: May 2019

e12027

Background: Peripheral neuropathy (PN) is a severe, dose-limiting toxicity of paclitaxel that occurs in up to 25% of patients and can lead to permanent loss of balance and manual dexterity. Due to the lack of effective strategies for PN prevention or treatment, there is a critical need to identify predictive risk factors for paclitaxel-induced PN. Vitamin insufficiencies are known risk factors for PN in other disease states. However, the effect of vitamin insufficiency on paclitaxel-induced PN has not been adequately investigated. Methods: Baseline levels of vitamin D and other nutrients (vitamin B, homocysteine, folate) were measured, and PN was assessed weekly in an observational trial of patients receiving paclitaxel 80 mg/m2 for 12 weeks for non-metastatic breast cancer (NCT0233811). Nutrient levels were measured by Michigan Medicine and insufficiency defined by institutional standards (vitamin D insufficiency < 20 ng/mL). In the primary analysis, the maximum increase from baseline in the 8-item sensory subscale (ΔCIPN8) of the EORTC CIPN20, a validated patient-reported PN assessment tool, was compared in nutrient insufficient and sufficient patients. The effect of vitamin insufficiencies on PN-induced treatment disruptions (dose decrease, delay, or discontinuation) was conducted as a secondary analysis. Results: Only vitamin D insufficiency was identified in enough patients for analysis (15/37 = 41%). Vitamin D insufficient patients reported a greater mean (+/- SD) ΔCIPN8 (36.39 ±22.8) than vitamin D sufficient patients (16.29 ±16.3) (p = 0.003). However, the increase in treatment disruption for vitamin D insufficient patients was not significant (OR = 2.98, 95% CI [0.72, 12.34], p = 0.16). Conclusions: Paclitaxel-treated patients who were vitamin D insufficient at baseline had greater increases in patient-reported PN. If validated in larger studies, vitamin D insufficiency may be a clinically translatable, modifiable risk factor that can be used to prevent paclitaxel-induced PN in patients with non-metastatic breast cancer.
Modeling the consequences of recurrences after trastuzumab treatment of HER2+ early-stage breast cancer.
Authors: Doan Quan V. , Martin Miguel , Lalla Deepa , Halperin Marc , Bryce Richard , Danese Mark D. , Moy Beverly
Published: May 2019

e12032

Background: The study objective was to estimate the long-term consequences of recurrences following treatment with trastuzumab (TRA) among women with HER2+ early stage breast cancer (BC) in the United States (US). Methods: A simulation model was constructed to estimate the following outcomes for each combination of hormone receptor (+/-) and nodal (+/-) status: number of recurrences, direct medical cost and indirect cost attributed to recurrences. The number of women aged ≥18 years with newly diagnosed HER2+ BC between 2018 and 2037 was estimated using SEER incidence rates (assumed constant over time) and from US Census data and accounted for the proportion of women utilizing adjuvant TRA by nodal status and age (assumed constant over time). The recurrence rate to any regional, distant or contralateral site was based on the long-term follow-up of the HERceptin Adjuvant (HERA) trial (expected 20-year recurrence proportions of 27.6% for TRA and 36.7% without TRA). Medical and pharmacy costs due to a recurrence were based on a 3-year study of metastatic BC patients treated with HER2 targeted agents. Beyond year 3, cost increased by 4.5% per year. The indirect costs of recurrences included loss of income from early retirement valued at the mean hourly wage, work absenteeism ($6,960/year), and reduced productivity while at work ($3,456/year). Non-cancer related mortality was estimated using SEER data. Results: We estimated that there would be 411,373 incident cases of early stage BC who would receive adjuvant TRA treatment from 2018 to 2037. Following each annual cohort for 20 years, we estimated that there would be 112,700 recurrences after TRA treatment and 149,674 recurrences without TRA treatment. The 20-year direct medical costs of recurrences were estimated to be $28.2 and $37.5 billion with and without TRA, respectively and the indirect costs were estimated to be $4.1 and $5.6 billion with and without TRA, respectively. Conclusions: Although TRA reduced recurrences by 25% in our 20-year model, there was a substantial number of recurrences. Future research will assess the clinical and economic impact of newer HER2 directed therapies in the adjuvant (pertuzumab, T-DM1) and extended adjuvant (neratinib) setting.
Impact of delaying initiation of adjuvant chemotherapy and trastuzumab in patients with early-stage HER2-positive breast cancer.
Authors: Fried Georgeta , Strulov Shachar Shlomit , Anani Sapir
Published: May 2019

e12033

Background: About 20% of breast cancers harbor an amplification and/ or overexpression of human epidermal growth factor receptor 2 (HER2).The treatment of HER2-positive BC combined of chemotherapy and Trastuzumab, results in reduction of disease recurrence in half. However, the optimal timing for adjuvant chemotherapy initiation is unclear. Methods: Retrospective chart review of 226 HER2-positive early-stage BC patients diagnosed between November 2002-May 2014 treated with adjuvant chemotherapy and Trastuzumab was obtained. Patients' average age was 54 years. Bivariate and multivariate analyses were performed to assess optimal timing for treatment initiation from primary diagnosis (obtained by tissue biopsy) and surgery. Primary endpoint was disease recurrence (locoregional/distant metastases). Other analysis included disease free survival (DFS), breast cancer specific survival (BCSS) and overall survival (OS). Results: Among 226 patients, 28 patients (12% of all patients) started Trastuzumab more than 36 weeks from primary diagnosis. The influence of a delay in treatment initiation was more profound as risk factors' number (e.g. stage, histopathological grade, positive lymph node status) increased, particulary with positive lymph nodes or a higher stage. 5-year disease free survival rates (DFS) in patients who had started Trastuzumab within than 36 weeks from diagnosis were: 93% in patient with 0-1 risk factors; 75% in patients with 2 risk factors; 77% in patients with 3-4 risk factors, and DFS rate dropped to 50% when Herceptin was initiated more than 36 weeks from diagnosis in patients with 3-4 risk factors. A higher disease recurrence rate (HR = 3.2 , p= 0.005,) was found in this subgroup, with highest negative impact in patients with stage III BC. A delay of more than 12 weeks from primary diagnosis to chemotherapy initiation in specific subgroups was attributed to a worse prognosis. The influence of treatment delay was more profound in patients with higher number of risk factors (e.g. stage, grade, positive lymph node (LN) status), particularly with positive LN or a higher stage. Conclusions: Delay in Trastuzumab initiation has a crucial negative influence upon DFS and OS rates, especially in specific subgroups with more risk factors. Delay of more than 12 weeks from primary diagnosis obtained by tissue biopsy to chemotherapy initiation may be associated with a worse prognosis.
Impact of chemotherapy sequence on the efficacy of scalp cooling devices for alopecia prevention.
Authors: Peña-Curiel Omar , Garza-Ledezma María Alejandra , Díaz-Pérez Héctor , Martinez-Cannon Bertha Alejandra , Canavati-Marcos Mauricio , Cardona-Huerta Servando , Villarreal-Garza Cynthia
Published: May 2019

e12034

Background: The use of scalp cooling devices (SCD) has been widely adopted for prevention against chemotherapy-induced alopecia (CIA). However, efficacy of SCD varies between different chemotherapy (CT) regimens. The aim of this study was to evaluate the effectiveness of SCD in breast cancer patients with different CT regimens treated in a tertiary cancer center in Monterrey, Mexico. Methods: All consecutive patients who used SCD were included. Data regarding treatment regimens and efficacy outcomes were prospectively collected. A descriptive analysis was performed to compare the effectiveness among the different CT regimens and sequences used. Results: We included a total of 49 patients with SCD usage from July 2016-January 2019. Table summarizes SCD efficacy, toxicities and CT regimens. In our study, 76% of patients had grade ≤1 CIA using SCD. 35% withdrew SCD use, with hair loss being the most common reason. 58% of patients who received upfront anthracycline-cyclophosphamide (AC) experienced grade 2 CIA. In contrast, no patients receiving taxane-only treatment had grade 2 CIA. Notably, only 3 of 16 patients (19%) who received upfront paclitaxel followed by anthracyclines developed grade 2 CIA. Conclusions: SCD proved to be highly effective in preventing grade 2 CIA with different CT regimens, including patients that received anthracycline-based regimens who started treatment with taxanes upfront. Accordingly, our results suggest that CT sequence, rather than type of CT agent may have a significant impact on the efficacy of SCD in CIA prevention. The results of larger studies are required to confirm our findings.[Table: see text]
Treatment and prognosis analysis of elderly patients with nonmetastatic triple-negative breast cancer.
Authors: Xiu Meng , Zhang Pin
Published: May 2019

e12038

Background: Treatment of TNBC in elderly women is limited by declining functional status and life expectancy. The impact of providing less aggressive treatment remains controversial. Methods: Data from patients aged ≥65 years with non-metastatic TNBC treated at Cancer Hospital of CAMS from 2010 to 2016 were included. The clinicopathological characteristics, treatment details and long-term survival were analyzed. Results: A total of 183 patients were enrolled. The median age was 69 years, and those ≥75 years old accounted for 23.0%. Of all the patients, 75.0% had chronic comorbidities, and 88.0% were invasive ductal carcinoma pathologically. Patients in stage I, II, III were 37.7%, 41.9%, 20.8%. Stage and age influenced chemotherapy or not independently. 42.0%, 34.7%, and 10.5% of patients with stage I, II and III had no chemotherapy and the proportion of chemotherapy decreased with age. 45.3% of patients had dose reductions during the treatment. At a median follow-up of 45 months, 28 patients (15.3%) had relapsed. The median RFS of patients relapsed was 23.5 months, 71.4% occurred within 3 years after diagnosis. Kaplan-Meier survival analysis estimated that the 3-year RFS and OS were 88.8% and 96.6%, and the 5-year were 84.0% and 92.8%. Multivariate Cox regression analysis (Table) showed that ≥6 cycles of chemotherapy, clinical stage, and lymphovascular invasion influenced prognosis significantly. Most patients received chemotherapy as AC-T/AT, AC/TC/T, or PCb, and RFS of subgroups had no difference obviously, as 3-year RFS were 87.5%, 76.5%, 93.2%. Compared to patients received no or <6 cycles of chemotherapy, the 3-year RFS of patients with stage I, II, and III who received ≥6 cycles of chemotherapy increased 4.4% (95.6% vs 100%), 1.3% (93.7% vs 95.0%) and 35.7% (34.3% vs 70.0%). Conclusions: There is insufficient treatment of non-metastatic TNBC in the elderly. The proportion of patients with stage I and II without chemotherapy is up to 40%, and the overall prognosis is not inferior obviously. We need more individualized treatment strategies for elderly TNBC.[Table: see text]
Chemotherapy-associated lipid changes in breast cancer patients: A retrospective analysis from a high-volume institution in China.
Authors: He Tao , Lv Qing , Wu Yunhao , Fan Yuan , Chen Jie
Published: May 2019

e12039

Background: Cytotoxic treatment may cause alterations in serum lipid of breast cancer patients but it remains controversial yet. The aim of this study is to investigate status of serum lipid pre- and post-chemotherapy as well as to compare lipid level alterations between different chemotherapy modalities. Methods: We retrospectively identified 1934 consecutive female patients who were surgically treated and pathologically diagnosed as breast cancer from February 2009 to December 2016 in a single institution. Results: There were 483(24.97%), 484(25.03%), 467(24.15%) and 500(25.85%) patients received AC-T, EC-T, TC and FEC chemotherapy regiment respectively. For the entire cohort, the levels of TG, TC and LDL were significant elevated in patients who received chemotherapy ( p＜ 0.01) while no significant difference was observed for HDL between pre- and post-chemotherapy. With chemotherapy regimens stratification, there were statistical significances with respect to TG, TC, HDL and LDL in AC-T, TC and FEC group between pre- and post-chemotherapy respectively ( p ＜0.05). Breast cancer patients with AC-T chemotherapy regimen increased TG value was higher than that of EC-T, TC, FEC regimens ( p ＜0.001) in premenopausal group. Moreover, utilizing of FEC regimen was associated with a significantly increased lipid level of HDL compared with the remaining regimens for both premenopausal and postmenopausal patients. Conclusions: Breast cancer patients receiving chemotherapy may carry a high risk of dyslipidemia. Therefore, regular lipid monitoring is very necessary for those breast cancer patients who receiving chemotherapy postoperatively.
Four versus six cycles of docetaxel and cyclophosphamide in early breast cancer.
Authors: Basu Aparna , Dabak Vrushali S. , Loutfi Randa , Ali Haythem Y. , Mohammed Hadi , Mahmood Sharmeen
Published: May 2019

e12047

Background: ABC trials established the use of non-anthracycline containing regimen, docetaxel and cyclophosphamide (TC) as adjuvant therapy in early breast cancer. In clinical practice, TC is commonly used in Stage I Triple Negative (TN) and Stage I,II Hormone positive breast cancer. However, no specific recommendations exist in literature, regarding the number of cycles that can be used. i.e. TC4 vs TC6. Our aim, was to determine if TC4 is non-inferior to TC6 when used as adjuvant therapy in early breast cancer. Methods: We retrospectively reviewed 143 patients who were diagnosed with early breast cancer, between 2007 to 2017, at our institution who had received either TC4 or TC6 as adjuvant therapy. The number of cycles the patients received were based on provider preference. The two groups (TC4, TC6) were compared in regard to stage of cancer at diagnosis based on AJCC 7th edition-stratified by TNM staging for hormone positive and T staging only for TN, grade of adverse events, recurrence and death from breast cancer. Median follow up was 5 years. Results: Out of the 143, 102(71.3%) received TC4 and 41(28.7%) received TC6. Among the hormone positive, 42 were stage I and out of which 32(76.2%) received TC4 and 10(23.8%) received TC6 and there were 24 stage II patients, out of which 17(70.8%) received TC4 and 7(29.2%) received TC6. Among the TN group, there were 64 who were T1, out of which 45(70.3%) received TC4 and 19(29.7%) received TC6, while there were 12 T2 patients, out of which 7(58.3%) received TC4 and 5(41.7%) received TC6. Recurrence of breast cancer was seen in 5(4.9%) in TC4 and 3(7.3%) in TC6, p=0.569. Death due to breast cancer was seen in 2(1.9%) in TC4 and 1(2.4%) in TC6, p=0.856. Adverse events were seen in 86(84.3%) in TC4 and 39(95.1%) in TC6,p=0.078. Adverse events of Grade 3 or higher were seen in 10(9.8%) in TC4 and 11(26.8%) in TC6, p=0.09. Conclusions: In this limited series, TC4 appears to be equally effective to TC6, with fewer adverse events of any grade and lower incidence of Grade 3 or higher side effects which was statistically significant. Although the proportion of patients who received TC 4 were higher in our series, the percentage of patients who received TC6 was higher in stage II for hormone positive and T2 for TN when compared to Stage 1 and T1 respectively. We also found a higher percentage of recurrence and death due to breast cancer in TC6 which was not statistically significant and this likely a reflection of the fact that as mentioned above patient with a higher stage at diagnosis tended to receive 6 cycles as compared to 4 cycles and therefore had a higher chance of recurrence in the future.
Variations in compliance with different endocrine therapies in ER-positive breast cancer in elderly females in a rural population.
Authors: Agbisit Christian , Johnson Alexander , Robinson Kathy , Delfino Kristin , Desai Meghna R.
Published: May 2019

e12052

Background: Compliance is a serious issue for breast cancer patients on endocrine therapy. There are various factors that may alter compliance across different age groups e.g. side effects, cognitive impairment, socioeconomic status etc. Noncompliance to therapy leads to early discontinuation and poor longterm outcome. The purpose of this study was to examine compliance rates with endocrine therapy i.e. aromatase inhibitors & tamoxifen in different age groups of geriatric breast cancer patients and determine its tolerability and impact on survival. Methods: An institutional database of a total of 269 patients with histologically confirmed invasive or in-situ breast cancer with age 65 years or older at the time of diagnosis was reviewed in an IRB approved fashion. Adjuvant endocrine therapy included tamoxifen, letrozole, anstrozole and fulvestrant. Patients were further subdivided into age groups. Compliance was measured as an early termination of therapy. Fisher’s exact test was used to calculate statistical difference. Results: Out of 266 eligible patients, 221 (83.1%) were offered endocrine therapy. 216 (81.2%) accepted endocrine therapy and 5 (1.9%) declined treatment. Distribution of each therapy was as follows:Anastrozole n = 90, (33.5%), Letrozole n = 88, (32.7%), Fulvestrant n = 6,( 2.3%), Tamoxifen n = 64, (23.8%). Early termination n = 44, (21.4%). Between the ages 65-70, n = 17,(18.had an early termination or noncompliance to therapy, in the age group from 71-80 age group,n = 24,(26.4%) had an early termination, and ages 81 and above,n = 3 (12.5%) had an early termination. There were no statistical differences between Anastrozole, Letrozole, Tamoxifen & Fulvestrant (P = 0.8275, P = 0.4589, P = 0.6136). There was also no statistical difference between age groups (P = 0.2742). Overall survival was worse with early termination,n = 20 vs not n = 6 but did not reach statistical significance ( P = 0.7). Conclusions: In breast cancer patients 65 and older, age can be a factor in noncompliance. However, in our study there were no correlation between age groups and compliance or with which drug used. Tolerability was similar between each endocrine therapy, across different age groups in this geriatric breast cancer population, in a rural setting.
Correlation analysis of radiotherapy and prognosis of elderly patients with hormone receptor-positive breast cancer in different immunohistochemical subtyping.
Authors: Zhang Jin
Published: May 2019

e12061

Background: Our study aimed to assess the effect of radiotherapy on the recurrence and survival in elderly patients with hormone-receptor-positive early breast cancer. Methods: We performed a retrospective analysis of 327 breast cancer patients who were 65 years or older with stage I-II, hormone-receptor-positive, after breast-conserving surgery and who received endocrine therapy(ET) or radiotherapy plus endocrine therapy(ET+RT). ET group was subgroup analyzed according to luminal A type and luminal B type, the same as ET+RT group. Evaluation Criterias were five-year local relapse rate(LRR),distant metastasis rate(DMR), disease-free survival rate (DFS) and overall survival rate (OS). Results: There were significant differences in five-year LRR (HR 3.33, 95% CI 1.51-7.34, P=0.0028) and DFS (HR 1.59, 95% CI 1.15-2.19, P=0.0045), but there were no significant differences in DMR and OS between the two groups. In luminal A type, there was no significant difference in five-year LRR, DMR,DFS, and OS between the ET group and the ET + RT group. In luminal B type, the difference was statistically significant in five-years LRR(HR 5.447, 95% CI 1.65-17.98, P=0.0054), DFS (HR 2.188, 95% CI 1.37-3.49, P=0.0010) and OS (HR 1.752, 95% CI 1.01-3.054, P=0.0478). In ET group, there were significant differences between luminal A type and luminal B type in five-years DFS (HR 1.841, 95% CI 1.23-2.75, P=0.0028) and OS (HR 1.763, 95% CI 1.07-2.91, P=0.0264). Conclusions: After breast-conserving surgery, radiotherapy can reduce the LRR and improve the DFS and OS of luminal B type elderly early patients, but luminal A type elderly early patients can not benefit from radiotherapy. Without radiotherapy, luminal A type patients have a better OS and DFS than luminal B.
“Good Risk”: low-risk patients with ductal carcinoma in situ (DCIS) benefit from whole breast radiotherapy after breast conservation surgery (BCS)–long-term follow-up.
Authors: Niwinska Anna , Galecki Jacek , Jagiello-Gruszfeld Agnieszka Irena , Michalski Wojciech
Published: May 2019

e12062

Background: Identification of patients group with low risk DCIS that do not require radiation therapy after BCS is still a challenge. We assessed recurrence rates in patients with „good risk” DCIS with and without radiotherapy after BCS, and subsequently compared our results with the long-term data from RTOG 9804 trial [1]. Methods: Out of 737 patients with DCIS managed between 1996-2011 at the Cancer Center Warsaw, Poland, 400 were treated conservatively. Out of those 133 were classified as „good risk” patients in accordance with RTOG 9804 trial criteria (DCIS < 2.5 cm, mammographically detected, NG1/G2 with margin = > 3 mm). 79 patients received only BCS and another 54 patients were treated with BCS and radiotherapy. Competing risk of recurrence, DFS and OS were calculated for both groups. The results were compared with the long-term observation results of RTOG 9804 trial. Results: The competing risk of recurrence after 10 years in the group treated with BCS and in patients receiving BCS with radiotherapy was 26% and 6% respectively (p = 0.013). 10-year DFS was 58% and 88% (p = 0.02) and OS was 94% and 97% (p = 0.3) respectively. Based on the ASTRO Conference 2018, 10-year recurrence risk without and with radiotherapy in RTOG 9804 trial were 9.1% and 1.7% [1]. In our study in comparison to RTOG 9804 trial results, more patients had DCIS sized 1.1-2.5 cm, excision margins of 3-9 mm and no patient received adjuvant tamoxifen. Conclusions: Similarly to the results of RTOG 9804 trial [1], radiotherapy reduced recurrence rate in “good risk” DCIS, however, in our study the recurrence rate was higher - probably due to difference in risk factors and no tamoxifen use. 1.McCormick B et al. Randomized trial evaluating radiation following surgical excision for “Good Risk” DCIS: 12year report from NRG/RTOG 9804. ASTRO October 21, 2018.
Time to surgery and overall survival after breast cancer diagnosis in a universal health system.
Authors: Eaglehouse Yvonne L , Georg Matthew W. , Shriver Craig D. , Zhu Kangmin
Published: May 2019

e12063

Background: It is unclear whether time between breast cancer diagnosis and surgical treatment is associated with survival. In the general U.S. population, timing of treatment and clinical outcomes may be related to access to care. We aimed to evaluate the relationship between time-to-surgery (TTS) and overall survival among women with a breast cancer diagnosis in the universal-access U.S. Military Health System (MHS). Methods: Women aged 18-64 who had a pathologic diagnosis of stages I-III breast cancer between 1998 and 2007 and who received breast cancer surgery during the primary course of treatment were identified in the Department of Defense’s Central Cancer Registry and MHS Data Repository linked databases containing records through December 31, 2008. The time in days between diagnosis and breast cancer surgery was calculated as TTS. Cox regression models were used to estimate hazards ratios (HR) and 95% confidence intervals (CIs) of all-cause death associated with TTS intervals of 0 days (diagnosis and surgery on the same day), 1-21 days (≤3 weeks), 22-35 days ( > 3-5 weeks), and 36 days or more ( > 5 weeks), controlling for potential confounders. Results: Women (n = 6,033) had a mean age of 50.1 (SD 9.3) years at diagnosis and an average follow-up of 3.8 (SD 2.1) years. The multivariable HRs (95% CIs) of all-cause death associated with TTS intervals were 1.26 (0.97, 1.63) for 0 days, 1.22 (0.94, 1.57) for 22-35 days, and 1.55 (1.18, 2.03) for ≥36 days compared to 1-21 days as the reference. The higher risk of mortality for TTS ≥36 days was observed among patient subgroups stratified by surgery type, age at diagnosis, and tumor stage. It was also shown that women with same-day surgery (TTS 0 days) had a significantly higher risk of all-cause mortality compared to the reference group among those age 18-49 at diagnosis (HR 1.52, 95% CI 1.03, 2.26). Conclusions: In the MHS, we found that longer TTS is associated with poorer overall survival after breast cancer while same-day surgery may also have a higher risk of mortality in some patient groups. Our findings suggest the importance of timeliness in receiving surgical treatment and the need for future research on factors related to TTS and its potential effects on clinical outcomes.
Preoperative conventional axillary ultrasound (AUS) and sonoelastography (SE) for predicting axillary lymph node metastasis in breast cancer patients.
Authors: Petrovsky Alexander , Khakurinova Nafset , Sholokhov Vladimir , Valiev Ramiz , Berdnikov Sergey , Samoylenko Igor , Amosova Victoria , Nechushkin Mikhail
Published: May 2019

e12074

Background: Patients with operable breast cancer (BC) and clinically negative lymph nodes (CNLN) usually undergo sentinel lymph node biopsy (SNLB) or axillary lymph nodes dissection (ALND). AUS followed by fine-needle aspiration (FNA) or core-needle biopsy (CNB) could decrease number of unnecessary SNLBs and allow to assign patient to ALND directly. On the other hand, new AUS techniques such as SWE could enhance AUS specificity and allow to avoid SNLB in some patients. Aim: To assess sensitivity, specificity and negative predictive value of the AUS+SWE followed by FNA or CNB in patients with operable BC. Methods: Since Sep 2012 to Jan 2018 150 pts with operable BC and were enrolled. We include 30 pts in training cohort with clinically positive lymph nodes to verify AUS+SWE sensitivity and specificity. In validation cohort only those pts who were candidates for SNLB and who presented with tumor staging up to T3, and clinically negative axillae were included (n=120). All patients underwent preoperative AUS in B-mode, SWE, followed by FNA or CNB in case of suspicious nodes were detected. All pts underwent axilla surgery (SNLB = 46, ALND =74) and final pathology outcomes were available for all pts. Results: In training cohort of 30 patients with clinically positive lymph nodes the overall AUS+SWE sensitivity was set at 89.2%. The positive predictive value was calculated to be 96.1%. In the assessment of invasive breast tumors stages T1- T3 with clinically negative lymph nodes the sensitivity was 74.2%, specificity 95.5% positive predictive value was 85.2% and negative predictive value 91.4% If FNA or CNB follow the AUS+SWE in patients with CNLN the sensitivity was 86.7%, specificity 85.7% positive predictive value was 92.8% and negative predictive value was 75% (FNA or CNB was performed in 40 patients of 120 in validation set). Area under the ROC-curve was calculated as 0.860 [95% CI 0.766 to 0.954] for the US+SWE and 0.705 [95% CI 0.581 to 0.828] for the US+SWE followed by FNA or CNB. Conclusions: Axillary US+SWE should be included in the preoperative staging of all patients with invasive breast cancer. The addition US+SWE (not obviously followed by FNA or CNB) could lead to avoiding of unnecessary SNLB or ALND in patients with clinically and pathologically negative lymph nodes with negative predictive value of 91.4%. On the other hand in patients with US+SWE positive lymph nodes SNLB could also be skipped and the time interval to definitive therapy became shorter. Clinical trial information: BCA_US_SWE_001.
Clinical utility of SERUM extracelullar domain of HER2 receptor (ECD) in HER2-positive breast cancer.
Authors: Gasol Cudós Ariadna , Morales Murillo Serafin , Veas Rodriguez Joel , Canosa Morales Carles , Olivé Jordi Melé , Salud Antonia
Published: May 2019

e12086

Background: Although ECD expression was validated as tumor marker years ago, it is not used in daily clinical practice even if a prognostic value was demonstrated in some trials. Methods: In our single institution, during January 2013-2019, ECD was analyzed in a series of HER2 positive breast cancer patients; 71 in early or locally-advanced and 45 in metastatic setting. Results: In the metastatic cohort, median ECD expression was of 28 ng/ml (6,5-350), thus 10 (22%) patients had lower levels than threshold of 15ng/ml. No correlation was found between ECD expression and other clinicopathological variables. No association was found with overall survival however in patients with metastases at diagnosis higher ECD expression was correlated with a short overall survival (25 vs 54 months). Higher levels of ECD decreased according to good response to treatment. Median ECD expression was of 12ng/ml (3,6-97) in non-metastatic setting, however only 11 (15%) patients had elevated levels ( > 15ng/ml). Estrogen receptor and ki67 expression were not correlated with ECD levels. Median ECD expression in tumors > 5cm was 21,87 ng/ml versus 12ng/ml in smaller tumors (p = 0,006); in nodal involvement median ECD was 16,77 ng/ml versus 12,05 without affectation (p = 0,09). Patients with ECD higher than 10 ng/ml had a 55% pathologic complete response (pCR) versus 25% if less than 10ng/ml (OR 3.68, p = 0.027). Interestingly, none of tumors > 5cm and ECD < 10ng/ml achieved a pCR. Conclusions: Higher levels of ECD were observed in the metastatic setting and their decreased levels during treatment was correlated with response. In early and locally-advanced setting higher levels were found in larger tumors; and also these tumors had better response than lower levels of ECD. ECD could be used as a monitoring tool in the metastatic scenario and as a predictive factor of response in the neoadjuvant setting, specifically in tumors > 5cm.
HER2-positive breast cancer: Combined 18F-FDG PET and CGFL/Curie nomogram to predict pathologic complete response after preoperative chemotherapy with trastuzumab.
Authors: Vincent Laura , Jankowski Clémentine , Cortet Marion , Arnould Laurent , Ladoire Sylvain , Coudert Bruno P. , Desmoulins Isabelle , Charon-Barra Celine , Beltjens Françoise , Rouzier Roman , Reyal Fabien , Humbert Olivier , Cochet Alexandre , Coutant Charles
Published: May 2019

e12095

Background: The aim of this study was to compare the value of 18F-fluorodesoxyglucose positron emission tomography (18F-FDG PET/CT) with CGFL/Curie nomogram to predict a pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in women with human epidermal growth factor 2 (HER2)-positive breast cancer treated by trastuzumab. Methods: Fifty-one women with HER2-positive breast cancer treated with trastuzumab plus taxane-based NAC, were retrospectively included from January 2005 to December 2015. For 18F-FDG PET/CT, the analyzed predictor was the maximum standardized uptake value of the primary tumor and axillary nodes after the first course of NAC (PET2.SUVmax). pCR was defined by no residual infiltrative tumor but in situ tumor was accepted. Accuracy of CGFL/Curie nomogram and PET2.SUVmax was evaluated measuring sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV). For each predictor, receiver operating characteristic (ROC) curve was created. To evaluate the correlation between predictors, the Spearman coefficient was calculated. Combined prediction was evaluated testing predictor’s associations. Results: For CGFL/Curie nomogram’s performances, Se, Sp, PPV and NPV were respectively: 76% (CI95%: 58-90%), 57% (CI95%: 43-66%), 55% (CI95%: 42-65), 77% (CI95%: 59-90%). For PET2.SUVmax’s performances, Se, Sp, PPV and NPV were respectively: 67% (CI95%: 48-81%), 77% (CI95%: 64-97%), 67% (CI95%: 48-82%), 77% (CI95%: 64-87%). ROC curves for these predictors were similar; the areas under the curve were 0.6 (CI95%: 0.56-0.64) for PET2.SUVmax and 0.55 (CI95%: 0.50-0.59) for CGFL/Curie nomogram. Spearman coefficient was 0.23. Combined prediction was more efficient with Se at 80%, VPN at 76%, Sp at 78% and VPP at 81 %. Conclusions: CGFL/Curie nomogram and PET2.SUVmax were two efficient predictors of pCR in patients with HER2-positive breast cancer. Combined prediction has an improved accuracy.
The diagnostic accuracy of 12-point core biopsy of a tumor bed compared to the study of surgically obtained breast tissue in patients with locally advanced triple-negative or HER2-positive breast cancer after neoadjuvant systemic and targeted therapy.
Authors: Krivorotko Petr , Yerechshenko Sergey , Dashyan Garik , Zhiltsova Elena , Bessonov Alexander , Tabagua Tengiz , Zernov Konstantin , Komyahov Alexander , Nikolaev Kirill , Gigolaeva Larisa , Emelyanov Alexander , Semiglazov Vladimir , Semiglazov Vladislav , Semiglazova Tatiana
Published: May 2019

e12097

Background: Innovative advances in neoadjuvant systemic and targeted breast cancer therapy implicate surgical treatment in specific patient groups can be avoided. The core biopsy of the tumor bed and some diagnostic approaches (breast ultrasound, mammography, SPECT/CT) allow for precise evaluation of the treatment efficacy. Methods: This research started in our department in 2018, we picked two groups of 15 patients each treated for locally advanced TNBC or grade cT1-4N1-3M0 HER2-positive breast cancer: HER2+/ER+ or HER2+/ER- breast cancer. The TNBC group received 6 cycles of NACT of paclitaxel combined with doxorubicin and carboplatin AUC5. The HER2+ group received 4 cycles of АС polychemotherapy followed by 4 cycles of monochemotherapy with the docetaxel and 3-weekly trastuzumab. The HER2+ group is receiving adjuvant trastuzumab for up to one year, where ER-positive patients are also given hormone therapy with tamoxifen or aromatase inhibitors. The response to neoadjuvant treatment was assessed in all patients using standard two-dimensional mammography, ultrasound elastography, and SPECT-CT. The 12-point core biopsy of a tumor bed was performed in the operating room setting by previously marked tumor projections. Then, all patients underwent either breast-conserving surgery or mastectomy with immediate reconstruction with expander/implant. Results: After neoadjuvant therapy, in a group of 15 patients with TNBC in surgically obtained material, the pathologic complete response (pCR) was observed in 8 patients (53.33%), whereas residual disease was found in 7 (46.67%) patients. The core biopsy results showed no tumor cells in 10 (66.67%) patients, and were detected in 5 (33.33%) patients (p = 0.0011), the accuracy of the method in this group was 80%. The overall response rate in the group of 15 patients with HER2-positive breast cancer was 8 (53.33%) patients with residual disease and 7 (46.67%) patients with pCR. According to core biopsy, tumor cells were present in 3 (20%) patients and were absent in 12 (80%) patients (p = 0.0787). Conclusions: Avoiding surgical treatment through not less than 12-point core biopsy of a tumor bed in patients with complete regression after neoadjuvant therapy is a new trend in the treatment of breast cancer. Any new approach in this sphere requires a long-term elaboration, compliance with the safety principles, rethinking standard procedures and following-up patients.
Comparative efficacy of neoadjuvant to adjuvant chemotherapy for the treatment of early-stage HER2 negative breast cancer: A population-based analysis.
Authors: LeVasseur Nathalie , Simmons Christine E. , Gondara Lovedeep , Speers Caroline , Diocee Rekha M. , Sun Julia , Nichol Alan , Lohrisch Caroline A. , Chia Stephen K. L.
Published: May 2019

e12100

Background: The use of neoadjuvant treatment has increased over the past decade due to its ability to assess tumour sensitivity to systemic treatment in vivo, and to downstage women for increased breast conserving surgery. Recent studies have stratified patients with residual disease to receive additional treatment, which has resulted in meaningful improvements in survival. However, meta-analysis data suggest similar long-term outcomes for patients treated with neoadjuvant chemotherapy (NACT) compared to adjuvant chemotherapy (ACT) in historical randomized trials. The comparative efficacy in a real-world setting utilizing modern chemotherapy regimens is unknown. Methods: A retrospective review of the BC Cancer Breast Cancer Outcomes Unit (BCOU) was performed to identify patients with stage I-III HER-2 negative breast cancer treated with chemotherapy at the BC Cancer Agency from 2005-2010. Patients were then divided into 2 groups: those who received neoadjuvant chemotherapy (NACT) and those who received adjuvant chemotherapy (ACT). A matched analysis (age, stage, subtype) for patients treated with NACT vs ACT (matched 1:3) was then performed using a propensity scoring method to compare distant disease-free survival (DDFS), breast cancer specific survival (BCSS) and overall survival (OS). No patients received adjuvant chemotherapy for residual disease after NACT. Results: A total of 656 patients met the inclusion criteria, consisting of 164 NACT and 492 ACT cases. Median age was 49 years (37-68) in the NACT group vs 49 (37-65) in the ACT group (p = 0.71). The majority had stage 3 disease, 64% in both groups (p = 1.0). Most were hormone receptor positive (HR+), 67.1% vs 70.7% in the NACT vs ACT groups, respectively (p = 0.41). 5-year DDFS was 75% with NACT (95%CI 67, 82) and 77% with ACT (95%CI 72, 81), p = 0.87. 5-year OS for patients treated with NACT was 77% (95%CI 71, 84) and 80% (95%CI 75, 85) for patients treated with ACT, p = 0.33. 5-year BCSS was 80% with NACT (95% CI 70, 86) and 82% (95%CI 77, 86) with ACT, p = 0.75. Multivariate analysis for tumour size, nodal involvement and subtype are ongoing. Conclusions: The use of NACT compared to ACT in a population-based setting did not result in significant differences in DDFS, OS or BCSS. Acknowledging the comparative efficacy of these approaches will be informative to determine if the addition of subsequent adjuvant treatment for patients with residual disease after NACT will lead to differential benefits in a population-based setting.