bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychological study of adolescent and young adult (AYA) cancer patients and their parents throughout and beyond their cancer treatment: A pilot study.
Authors: Hatcher Helen , Lack Carole , Walsh Cathy , Abbas Laura , Fretwell Jo , Moss Wendy , Dobson Nicky , Goodyer Ian , Alam Salma
Published: March 2020

9589

Background: The cancer journey for an AYA is often complicated by diagnostic delays, poor prognosis and negative physical and psycho-social consequences. Distress of young patients and survivors is often overlooked and the real incidence of psychopathology remaining hidden. We aimed to understand the psychological impact and identify which factors most affect the patient experience. Methods: 172 patients on the Cambridge AYA register were invited to take part. Patients were asked to complete 2 questionnaires, SCL90 and RSQ, measuring psychological symptoms and response styles respectively, and to take part in a semi-structured interview. Parents were asked to complete the York Survey and be interviewed. Results: 33 patients and 45 parents/others were recruited. Questionnaires completed: 33 SCL90 and RSQ; 42 York Survey. Interview data from: 23 patients, 26 parents, 3 others. Patient sample: 16 male, 17 female; mean age (recruitment) = 20.76 (16-26); age (diagnosis) = 17.26 (12-24). Diagnoses evenly distributed across solid and haematological malignancies. All patients had experienced significant levels of psychological distress at some point in their cancer journey. 51% reached caseness on the SCL90 (showed a symptom profile consistent with a high risk of a disorder). Caseness increased with age and was correlated with higher rumination scores. Positive influences included family, friend and peer support, good communication and support from the AYA service and specialist nurses. Negative influences included delayed diagnosis, poor communication styles, anxiety about long term effects and lack of appropriate psychological support. Conclusions: We have shown evidence of elevated psychological symptoms in this population. Patients and their families have prioritized clear needs; early diagnosis, high quality of information and communication, access to psychological help at each stage and post treatment help in gaining independence and planning for a positive future. We should work towards meeting these needs for this vulnerable group.
The value of personalizing medicine: Medical oncologists’ and patients’ perspectives on genomic testing of breast tumors in chemotherapy treatment decisions.
Authors: Trudeau Maureen E. , Bombard Yvonne , Rozmovits Linda , Leighl Natasha B. , Deal Ken , Marshall Deborah
Published: March 2020

e11000

Background: Benefits of adjuvant chemotherapy for early-stage breast cancer patients (pts) depend on baseline recurrence risks. Gene expression profiling (GEP) of tumours informs baseline risk prediction, potentially reducing unnecessary treatment and healthcare costs. Limited evidence exists on its clinical utility; we explored pts and medical oncologists (MO) perspectives on GEP in chemotherapy decisions. Methods: We used a qualitative design of individual interviews with MO (n=10), focus groups and individual interviews with pts (n=20) from Ontario. Pts who underwent genomic testing of their tumours (‘OncotypeDx’), were recruited through clinics from two academic hospitals in Toronto. MO were recruited through clinics, advertisements and referrals from the research team. Data were analyzed using interpretative qualitative methods, including content analysis, qualitative description and constant comparison techniques. Results: Pts and MO valued GEP as an additional decision-support tool, complementing existing clinical indicators. Its perceived utility varied between pts and MO. Pts valued the test highly, suggesting it was one of the primary determinants of their treatment decision. All pts followed the course of action their results suggested. Pts with intermediate scores often used the results to reinforce their pre-existing treatment preferences. MO were mixed about the test’s utility. Some considered it another tool supporting their approach to risk assessments, while others used it more definitively to resolve their uncertainty. MO explained the test’s contribution to decision-making but remained uncertain about pts understanding and expectations of the test. Some raised concerns about the variability of its use and interpretation within their medical community. Conclusions: Pts and MO valued the test, often using it as a primary determinant in their treatment decision, despite MO concerns about its technical limitations and pts limited understanding. Results identify a need for informational decision aids and practice guidelines to support pts understanding and standardized application of the test.
Characterization of patients who received further adjuvant endocrine therapy after 5 years of aromatase inhibitors (AIs): NCIC CTG MA 27.
Authors: Vogl Steven E. , Altwairgi Abdullah Khalaf , Chapman Judy-Anne W. , Zhu Liting , Shepherd Lois E. , Goss Paul Edward ,   NCIC Clinical Trials Group
Published: March 2020

e11005

Background: MA.27 examined the efficacy of 5 yrs of adjuvant aromatase inhibitors (AI), exemestane and anastrozole. Long term outcomes of AI trials may be influenced by unspecified subsequent hormonal therapy so we enquired about its frequency. Methods: Clinical trials (NCIC CTG MA.17R, NSABP B-43) are exploring >5 yrs AI; neither efficacy nor toxicities are known. MA.27 enrolled 7,576 patients June 2003 to July 2008: 5526 (73% in US), 1301 (17% in Canada), 749 (10% outside North America). Clinical cut-off for final follow-up and analysis was April 15 2010: median 4.1 yrs follow-up. Receipt of concomitant medications was routinely reported throughout the trial. Only 345 patients (median age, 64.2 years) completed protocol-specified 5 yrs AI, without breast cancer (BC) relapse, development of contralateral BC, or other second malignancies. Patients were classified by extended endocrine therapy: off trial, physician prescribed specific endocrine therapy; randomized trial endocrine therapy; or no endocrine therapy. Differences in baseline patient and tumor characteristics for these classifications were compared with Fisher’s exact test. Results: From the total group of 345 patients, 320 (93%) received no further endocrine therapy, and 25 (7%) received subsequent therapy. Among the 25, 18 (72%) entered trials and were assigned to endocrine therapy or placebo. Physicians prescribed endocrine therapy to the other 7 (28%). Fourteen (78%) of those who received trial assigned and 7 (100%) of those who received specific additional endocrine therapy were below 70 years of age. Of the 25 patients who received subsequent therapy, only 2 (8%) had >2 cm tumor, and 6 (24%) had node positive tumors. None of the characteristics were significantly different for women who did or did not receive additional therapy. Conclusions: MA.27 is closed to further follow-up, so these results represent the totality of trial information about further endocrine therapy from clinical practices of those who enrolled MA.27 patients. It appears that subsequent hormonal therapy was uncommon (7% of women) after 5 yrs of an AI.
Combination treatment with aromatase inhibitor and capecitabine as first- or second-line treatment in metastatic breast cancer.
Authors: Alvarado Miranda Alberto , Limon Jesus , Medina Fernando Lara , Arce Claudia , Zinser Juan Wolfgang , Bargallo Rocha Enrique , Villarreal-Garza Cynthia Mayte
Published: March 2020

e11016

Background: Preclinical studies have shown that the combination of an aromatase inhibitor (AI) and oral fluoropyrimidines in estrogen receptor (ER)-positive cell lines enhance antitumor efficacy. This might be explained by reduction of ER-induced growth signaling in addition to decrease in estrogen production. This retrospective analysis of a cohort of patients with metastatic breast cancer (MBC) evaluates the efficacy and safety of combined AI with capecitabine. Methods: Patients with hormone receptor-positive MBC treated with this combination were evaluated and outcomes were compared to women treated with capecitabine (conventional dose) or AI as monotherapy. The administered total dose of capecitabine was 2000 mg. per day in combination with AI. Results: Of 93 patients evaluated, 37 received the combination treatment, 27 capecitabine and 29 an AI. Combination was used in 26 patients as first-line treatment and 11 as second-line. At the time of progression, 92% had a performance status of ≤2 and 58% of patients had visceral disease. No significant difference was observed between the three groups according to clinical and pathological features. Mean follow-up was 23 months (m). The median PFS of first-line treatment was significantly better for the combination (PFS not-reached vs.3.0 m for capecitabine and 13.0 m for AI, p<0.0001). For second-line treatment, the PFS was longer in the combination compared to capecitabine and AI (PFS not reached vs. 6.0 m vs.13.0 m, respectively, p=0-041). For the entire cohort, OS was not reached. The most common adverse events for the combination group were grade 1 and 2 hand-foot syndrome (65%), grade 1 fatigue (52%) and grade 1 diarrhea (5%). Only one grade 3 hand-foot syndrome event was reported. Conclusions: Combination treatment with capecitabine and AI used as first-line treatment or second-line improved PFS compared to treatment with either single agent. The combination was safe and rendered dismal toxicity. Prospective randomized clinical trials should evaluate the use of the combination of capecitabine and an AI in advanced breast cancer in order to confirm our findings.
Evaluation of the prognostic value and phenotypic determinants of Bcl-2 expression in breast invasive carcinoma.
Authors: Luengo Maria Isabel , Garcia-Garre Elisa , Martinez-Diaz Francisco , de la Morena Pilar , Garcia-Martinez Elena , Castaño Patricia , Luengo-Gil Gines , Vicente Angeles , Ortuño-Pacheco Guzman , Vicente Vicente , Ayala Francisco
Published: March 2020

e11024

Background: Bcl-2 expression has been related to hormonal dependence and better prognosis of breast cancer. Although some reports suggest that its expression has an independent prognostic value, especially in N positive patients, the clinical relevance of determining Bcl-2 is unclear. The aim of this work was to analyze which other tumor markers predict Bcl-2 expression in breast cancer and explore its prognostic value. Methods: Immunohistochemical expression of ER, PR, Her2-neu, Ki-67, p53, cathepsin-D and Bcl-2 was prospectively examined in a series of 87 consecutive invasive BC patients. Bcl-2 was semiquantitavely scored according to a validated system (Treré, 2007). Correlation between variables was analyzed with Chi-square test; disease free (DFS) and overall survival (OS) were analyzed by log-rank test and Cox models. Results: Patient characteristics: median age 57 yrs (31-86), 64.5% postmenopausal; treatment: 49.5% breast-preserving surgery, 71.6% adjuvant-neoadjuvant chemotherapy, 72.1% adjuvant radiotherapy ; tumor histology: 83.9% ductal invasive carcinoma, 28.2% grade 3; stage: T1:57%, T2:31.2%, T3-4:8.6%, 48.9% nodal metastasis (pN1:36.7%; pN2:12.2%); tumor phenotype: 77.2% ER+ , 78.3% PgR+ , 9.7% Her2-neu+, 50.6% high Ki-67 (>13%). Immunohistochemical evaluation for Bcl-2: 41/87 (47.1%) positive cases. No expression of Bcl-2 was observed in ER/PgR negative tumors (p< 0.001). Bcl-2 expression was associated to histological grade 1-2 (p=0.009), absence of Her2-neu amplification (p=0.03), p53+ status (p=0.008) and lower cathepsin-D expression (p<0.001), but no association was found for proliferation (Ki-67) or stage (pT or pN). A significant effect of Bcl-2 on overall (p=0.27) or disease free survival (p=0.28) was found neither in the whole group nor in pN+ or pN- subgroups. The only independent prognostic factors for DFS were hormone-sensitivity (OR: 0.10; p=0.009) and pN (OR=2.77; p=0.05). Conclusions: Expression of Bcl-2 in invasive breast cancer seems to be dependent on hormonal sensitivity, p53 status and Her2 expression; no independent prognostic value for recurrence or survival was found in our series.
Outcomes for elderly breast cancer patients in Louisiana.
Authors: Ruiz Marco A , Reske Tom
Published: March 2020

e11030

Background: Elderly breast cancer patients, compared to younger breast cancer patients, are diagnosed with a higher stage of disease. They are also found to undergo less surgery, receive more frequently hormonal treatment and have decreased relative survival. The interest of this study was to examine if differences in treatment and survival between >65 year old and <65 year old patients in Louisiana. Methods: The SEER database was searched and all cases of female breast cancer in the state of Louisiana between 2000 and 2008 were analyzed. Data was stratified by age group and year of occurrence. SEER definitions for breast cancer, surgery, chemotherapy, elderly, young populations, radiation therapy, breast conservative surgery were applied. Results: The state prevalence of localized breast cancer is lower compared to the national rate (128.5 vs. 144 p <0.001). The rate of regional breast disease is much higher in Louisiana patients than national average rate (69.7 vs. 57.9 p <0.001). There is no difference in disseminated disease. When the elderly group is compared to non-elderly group there was a difference in localized disease (non-elderly 59.9% vs. elderly 64.98 P<0.001). There was a difference also in regional disease (non-elderly 33.75% vs. elderly 25.02%). No difference was noted in rates of disseminated disease (non-elderly 5.03% vs. elderly 5.77%). The elderly group was offered less surgery compared to the young group (11.39% vs. 6.68% in the young group, p<0.005). In terms of radiation therapy the elderly group receive more general radiation interventions than the young group (65.97% vs. 53.86 p <0.005). In relation to type of radiotherapy (beam radiation and radioactive implants) there were no differences between the two groups. Mortality rates for the elderly group was higher in Louisiana compared to the national average. This difference was more remarkable in the >85 age group (127.8 vs. 118.5, p<0.001) Conclusions: Differences in treatment modalities and management interventions between young and elderly breast cancer in Louisiana patients were observed. Mortality is higher among elderly breast cancer patients in Louisiana compared to national average. Further studies are needed to review the these regional differences.
A multicenter, open-label phase II trial of liposomal doxorubicin (LD) and docetaxel (DX), followed by concurrent chemotherapy and radiation therapy in locally advanced high-risk, early breast cancer (HRBC).
Authors: Recchia Francesco , Candeloro Giampiero , Cesta Alisia , Desideri Giovambattista , Necozione Stefano , Rea Silvio
Published: March 2020

e11041

Background: Taxanes and anthracyclines (ANs) are among the most active agents in the treatment of breast cancer. However, ANs are associated with dose-related cardiac toxicity, which can lead to progressive myocardial damage. Non-pegylated liposome-encapsulated doxorubicin (Myocet®), has been shown to significantly reduce cardiac toxicity even though providing comparable antitumor efficacy. Primary endpoint of this phase II study was the assessment of early and late cardiac toxicity of young patients with HRBC treated with LD and DX. Secondary end-points were the incidence of hematological toxicity, time to progression and overall survival in this cohort of patients. Methods: From 05-2006 to 10-2009, 60 HRBC patients were entered into the study. They were treated with LD 60 mg/m2 and DX 75 mg/m2 every three weeks for six courses. Hematological growth factors were given when indicated. Cyclophosphamide 600 mg/m2, methotrexate 60 mg/m2 and 5-fluorouracil 600 mg/m2 were given for six courses concomitantly with radiation therapy to the breast, axilla and supraclavicular nodes. After chemo-radiation therapy, a hormonal therapy was given to estrogen receptors positive (ER+) patients and trastuzumab to Herb-2 positive patients. LVEF was evaluated at baseline and after 6 months, thereafter, up to 5 years. Results: Median age was 49 years. Mean number of positive axillary nodes was 4.9 (range 0-20). 70% were ER+, 30% were ER - and progesterone receptor (PGR) negative. Median Ki-67 was 30% (range 20%-100%), 18% of patients were Herb-2 positive and 18% of patients had pre-existing hypertension. Delivered dose was 95.7% of the planned dose. No patient showed neither a decrease of EF > 10%, nor congestive heart failure. Febrile neutropenia was observed in 12% of patients. At 44 months of median follow-up, 86% of patients were disease-free and 94% were alive. Conclusions: Chemotherapy with LD and DX has shown low cardiac toxicity and high activity in this group of HRBC patients.
Overexpression of Notch-1 induced tamoxifen resistance through down regulation of ESR1 in positive estrogen receptor breast cancer.
Authors: Yousif Nasser Ghaly , Al-Matwari Majid
Published: March 2020

e11046

Background: Tamoxifen is one of the most widely used drugs in the treatment of estrogen-receptor positive breast cancer, and acquired resistance to tamoxifen during treatment are largely unknown and recent research showed that lower levels of ESR1 associated with tamoxifen resistance in ER-positive breast tumors, from other hand highly expression of Notch-1 and/or Jagged-1 has negative prognostic significance in breast cancer, in this study we show the cross-talk between Notch and the lower levels of ESR1 estrogen receptor positive breast cancer. Methods: A retrospective study with clinico-pathological analysis of 195 patients had ER-positive breast cancer used tamoxifen as an adjuvant systemic therapy, gene expression profiling of paraffin-embedded tumors for ESR1, Real-time PCR and Western blot analysis were performed to detect Notch-1/Jagged-1. Results: From 195 patients 32% had tamoxifen resistance which related with lower levels of ESR1 expression (P=0.019) and there was, a highly significant association of over expression Notch1 protein with the lower levels of ESR1 (P=0.006). Conclusions: The results from this study demonstrate for the first time that Notch-1 regulate levels of ESR1 in ER-positive breast cancer, and partly responsible for tamoxifen resistance, the Notch signaling pathway may be a potential therapeutic target beside current breast cancer therapy and need further investigation to know the mechanism of this pathway.
Concordance between independently and investigator-assessed progression-free survival in CLEOPATRA.
Authors: Miles David , Swain Sandra M. , Im Young-Hyuck , Knott Adam , Ross Graham , Clark Emma , Benyunes Mark , Baselga José
Published: March 2020

e11055^

Background: In CLEOPATRA, pertuzumab (P) + trastuzumab (T) + docetaxel (D) was compared to placebo (Pla)+T+D in HER2-positive 1st-line MBC. In MBC trials, PFS rather than overall survival is often defined as the primary endpoint as PFS data are available earlier and later-line therapy does not impact results. The primary endpoint in CLEOPATRA, PFS, was assessed by an Independent Review Facility (IRF), with investigator (inv)-assessed PFS as a secondary endpoint. As a measure of consistency and robustness, concordance between IRF- and inv-assessed PFS was analyzed. Methods: PFS was defined as time from randomization to first documented radiographic evidence of progressive disease (PD) or death from any cause within 18 wk of the last IRF tumor assessment. Tumor assessments took place every 9 wk and continued until IRF-confirmed PD. Treatment decisions were solely based on the inv’s assessment of PD. Indicators of concordance between IRF- and inv-assessed PFS included: PFS event by IRF only; PFS event by inv only; PFS event by IRF and inv; no PFS event by IRF and inv. These indicators were assessed at any time on study, within 30 d or within 9 wk. Several pre-specified sensitivity analyses for PFS were also performed. Results: 808 pt were enrolled and central tumor assessments performed for 781 pt. Compliance with the schedule of tumor assessments was generally high and comparable between arms, with >78% of pt undergoing assessments within 7 d of the scheduled visit over the 1st yr. At any time on study, concordance between IRF- and inv-assessed PFS was 85%. Of the 15% discordant cases, an equal proportion was assessed by the IRF as a PFS event but not by the inv and vice versa. Estimates of the median time to PFS event based on IRF and inv assessments were identical, Pla+T+D: 12.4 mo, P+T+D: 18.5 mo (IRF: HR 0.62, P < .0001; inv: HR 0.65, P < .0001). Conclusions: Concordance between IRF- and inv-assessed PFS was high, supporting consistency and robustness of the PFS analyses. The subjective nature of PD and potential for bias were reduced by the double-blind, placebo-controlled study design; RECIST 1.0 criteria; identical schedule of assessments in both arms; IRF review and continuation of tumor assessments until IRF confirmation of PD.
Nine-weeks of adjuvant trastuzumab in HER2-positive breast cancer: A single center experience.
Authors: Kizilarslanoglu Cemal , Petekkaya Ibrahim , Babacan Taner , Altundag Kadri
Published: March 2020

e11080

Background: Trastuzumab is an effective adjuvant targeted therapy in patients with HER-2 positive breast cancer. However, effect of this therapy on survival is not well described in literature. In this study, we aimed to show characteristics of patients treated with nine week trastuzumab therapy for breast cancer and survival analysis. Methods: We analyzed the data of 2.218 breast cancer patients treated and followed up in our medical oncology department. There were 165 patients treated with 9 weeks of adjuvant trastuzumab therapy in this cohort. Patients’ characteristics, prognostic factors, and survival data were analyzed by using SPSS 18.0 version. Results: The mean age of the patients at the time of diagnosis of breast cancer was 47.3 ± 10.0 years. Sixty two (37.6%) patients were postmenopausal, eighty two patients (49.7%) were premenopausal and twenty patients (12.1%) were peri-menopausal. Invasive ductal carcinoma was the most common pathological type and was observed in 87.9% of the patients. ER and PR was positive in 49.1% of the patients and 54.5 % of the patients, respectively. Percentage of stage of the patients was 10.9 in stage I, 21.1 in stage IIA, 17.6 in stage IIB, 21.2 in stage IIIA, 0.6 in stage IIIB, 23.6 in stage IIIC. Mean follow up time of the patients was 30.9 ± 13.4 months. Numbers of the patients with progression were eighteen (10.9%). Eight (4.8%) patients died due to disease progression. Two-year survival rate was 98.3%. Disease free, progression free and overall survival times could not be obtained due to inadequate number of events. Conclusions: The superiority of nine weeks of adjuvant trastuzumab therapy to standard one year regimen of adjuvant trastuzumab is not well described in literature. The studies comparing 9-weeks and one year of adjuvant trastuzumab use with large numbers of patients are needed to show which regimen is superior.
Randomized pilot study of a weight gain prevention intervention for breast cancer patients receiving neoadjuvant chemotherapy.
Authors: Basen-Engquist Karen , Murray James L. , Baum George , Gutierrez-Barrera Angelica M. , Arun Banu
Published: March 2020

e11090

Background: Weight gain is a common problem after breast cancer diagnosis and treatment, particularly for women who receive chemotherapy. The weight gain has negative effects on quality of life, increases risk for chronic disease, and may increase risk of breast cancer recurrence. This pilot study tested a behavioral weight gain prevention intervention on weight, IGF-I, and IGFBP-3. Methods: Thirty-nine breast cancer patients receiving neoadjuvant chemotherapy were randomized to the weight gain prevention intervention or usual care. The intervention focused on exercise (resistance training, aerobic) and eating a low energy dense diet. Participants received 20 sessions during chemotherapy (14 in person and 6 by telephone) and 9 sessions after surgery (3 in person, 6 by telephone). They completed weight and other assessments at baseline (t0), mid-chemotherapy (T1), post-chemotherapy (t2), post surgical recovery (T3), after the post-surgical intervention (T4) and long term follow-up 6-9 months post surgery (T5). Serum was collected at T0, T2, T3, and T5 and analyzed for IGF-I and IGFBP-3. Results: Controlling for baseline weight, the intervention group weighed less than the control group at T1-T4, a result which approached significance (p=.08) in the intent to treat analysis. There was also a significant obesity x treatment group interaction, indicating that the intervention was most effective for patients who were obese at baseline (p=0.03). The groups did not differ in weight at the post-intervention follow-up (p=0.839). There was no significant difference between the groups in IGF-I or IGFBP-3. Conclusions: A diet and exercise intervention delivered during and after chemotherapy can promote weight loss in breast cancer patients, but the results may not be sustained after the intervention ends. [caption]Participants’ weights in kilograms, adjusted for baseline weight (least squares means).[caption] [Table: see text]
NFATc1 protein expression and its relationship with clinical characteristics in breast cancer.
Authors: Kang Xinmei , Wang Shuhuai , Song Ying
Published: March 2020

e11095

Background: The nuclear factors of activated T cells (NFATs) have been previously studied in the immune system as transcription factors during the activation of T lymphocyte. In the recent years, emerging evidences have showed that they may play an important role in the development and progression of human cancer. In this study we investigate NFATc1 protein expression and its relationship with clinical characteristics in breast cancer. Methods: NFATc1 protein expression was determined by immunohistochemical analysis in 86 surgically resected breast cancer samples between Jul 2004 and Jun 2006. The relationship between NFATc1 expression and clinical characteristics of breast cancer was analyzed by multivariate logistic regression and survival analyses. Results: NFATc1 protein was significantly overexpressed in breast cancer tumor cells compared with the matched normal tissues. High expression of NFATc1 proteins was associated with high tumor grade, lymph nodes involved and shorter disease free survival (P<0.05), but there was no correlation between NFATc1 protein expression and tumor size, hormone receptor status or overall survival (P>0.05). Conclusions: This study suggested that high NFATc1 expression was present in breast cancer and it might be involved in the process of cancer development and related to poor prognosis of breast cancer.
Safety and efficacy of eribulin in patients with advanced breast cancer treated outside of a clinical trial: A single institution experience.
Authors: Kessler Luisa , Bergh Jonas , Foukakis Theodoros
Published: March 2020

e11510

Background: Eribulin is a non-taxane, microtubule dynamics inhibitor that was approved for the treatment of patients with metastatic breast cancer (MBC) in Europe in March 2011. Experience with routine use of eribulin is limited. Methods: All patients receiving eribulin at the Oncology Department, Karolinska University Hospital outside of a clinical trial are treated according to the approved indication and dosology. For the purpose of an internal quality control, treated patients are registered in a database. All patients registered at the time point of the analysis were evaluated for safety and efficacy. Treatment toxicity including fatigue, neurotoxicity and infection was graded according to CTCAE v4.0. Efficacy was investigated using the routinely performed radiological assessments. Results: To date, twenty patients have received a total of 104 cycles of eribulin. All patients were heavily pretreated with a median of 3 (range 1-6) previous chemotherapy lines for MBC. The median age of the patients was 54 years (range 35-74). Fourteen patients are alive and 12 are still undergoing treatment with eribulin. No hypersensitivity reactions and no toxic deaths were seen. Fatigue was observed in 45% of the patients (grade 3 20%), while 20% experienced neurotoxicity and 35% were treated for an infection (grade 3 20%). None of the patients experienced grade 3 neurotoxicity. Interestingly, 3 cases of Herpes zoster reactivation were observed. Fifteen of the patients have been radiologically assessed at the time point of the analysis. Six of those patients had partial response (PR), one patient had complete response (CR) and one patient had stable disease (SD). Seven patients had progressive disease (PD). Conclusions: Eribulin administered outside of a clinical trial in patients with advanced breast cancer was safe and well tolerated. Although the majority of the patients were heavily pretreated, objective response was seen in nearly half of the cases.
Clinical and pathological characteristics of triple-negative breast cancer patients: A single-center experience.
Authors: Akdeniz Aydan , Yalcin Selim , Rahatli Samed , Kucukoztas Nadire , Yagmurdur Mahmut Can , Dizdar Omer , Altundag Ozden , Ozyilkan Ozgur
Published: March 2020

e11515

Background: Triple negative breast cancer in which estrogen, progesterone receptors and c-erbB2 overexpression are negative, seems to have different clinical course and recurrence pattern. Methods: We evaluated retrospectively clinical demographic and pathological characteristics of triple negative breast cancers and investigated the association of these characteristics with OS and PFS. Results: 59 early stage patients with triple negative breast cancer patients followed in Baskent University Hospital between 1997-2009 were enrolled into the study. The median age of patients was 49. Median follow-up duration was 27 months (0.27-132 months). Two patients died during the follow-up. Invasive ductal carcinoma pathology was reported in 38 patients, invasive lobular in 3 patients, medullary in 5 patients.Almost half of the patients had LVI. 79% of patients had a T2 disease. 30% of patients’ tumor histological grade was III. Cancer history in the family was present in 95% of patients. Almost half of the patients had stage II disease. Adjuvant chemotherapy was given to 43 patients. Relapses were observed in 15 patients.The most common metastatic site was lung. Patients having high grade tumor, >3 (+) lymph nodes, younger age have higher chance of relapse during follow-up. Conclusions: In accordance with the literature, our triple negative breast cancer patients showed more aggressive characteristics. Although median follow-up is short, one-fourth of the patients having recurrence support natue of the triple negative breast cancer patients. In our study, triple negative patients had younger age at diagnosis, high grade tumors and more tendency to metastasize to visceral organs.
Weekly docetaxel in patients with metastatic breast cancer: A Bangladeshi perspective.
Authors: Hoque Ehteshamul , Karim Shanaz , Ahmed Rakib Uddin
Published: March 2020

e11533

Background: Docetaxel has demonstrated high antitumor activity in first and second line treatment of metastatic breast cancer. Usually it is administrated three weekly at a dose of 75mg/ m2. We evaluated the efficacy and toxicity of Docetaxel in metastatic breast cancer in weekly bases. This study analyzed the efficacy and toxicity of docetaxel given weekly. Methods: Thirty eight patients with metastatic breast cancer received docetaxel, 35 mg/m2 weekly for six weeks, followed by two weeks interval. Additional cycles (three weeks' treatment, two weeks' rest) were given until disease progression or death. All patients had received prior chemotherapy. Of them 32 patients previously received anthracycline-containing regimens and 5 patients had received taxane based regimens. Results: Out of thirty eight patients thirty seven were evaluable. There was one complete response (3%), 11 patient has partial responses (30%), 17 patients with stable disease (46%) and six with disease progression (16%). Overall response rate was 78%. Median progression-free survival was 9.2 months. Three patients showed grade 3 neutropenia. 14 showed grade 3 alopecia, and various grade 1–2 non-haematological toxicities were observed. Treatment was delayed in two patients due to haemalotoxicity and stopped in one patient due to painful nail toxicity. Conclusions: Docetaxel is effective in three weekly regimens. In our study we found weekly docetaxel is as effective as the previous regimen. The efficacy of weekly docetaxel (35 mg/m2) can be an effective schedule for metastatic breast cancer who has received chemotherapy previously. The toxicity in this regimen is very low and manageable.
AVALUZ study: First line with bevacizumab in combination with paclitaxel (P) and gemcitabine (G) in patients with HER2-negative or recurrent mBC: OS analysis.
Authors: Salvador Javier , Ciruelos Eva M. , Codes Manuel , Jaen Ana , Gil Miquel , Galan Antonio , Murias Adolfo , Jara-Sanchez Carlos , De la Haba- Rodriguez Juan , Baena Jose Manuel , Villanueva Silva Maria Jose , Bayo Juan L. , Blancas Isabel , Gonzalez Encarnacion , Perez Diego , Mel Jose Ramón , Manso Luis
Published: March 2020

e11535

Background: The combination of bevacizumab (B) with taxanes, capecitabine or anthracyclines has shown increased PFS in pts with mBC. The combination with G and P has been evaluated and has demonstrated high response rate and good toxicity profile. The aim of this study is to evaluate the efficacy and toxicity profile of the combination of B with G and P, providing the final result of PFS, update of OS and the toxicity experienced in all pts treated. Methods: A phase II multicenter, national, open-label study in pts diagnosed of recurrent or metastatic HER-2 negative BC, treated with first line B 10 mg/kg, P 150 mg/m2 and G 2000 mg/m2 day 1 and 15 c/28 d until progression disease, unacceptable toxicity or medical decision. This abstract evaluates efficacy by PFS as primary endpoint and as secondary endpoints: OS, response rate and toxicity profile (NCI CTC v3.0 criteria). Results: From January 2009 to December 2009, 82 evaluable pts were recruited in 23 sites. The characteristic of the all of pts included (90) are: median age 51.5 (26-81), ER + 68%, PR + 59%, triple negative pts 19%, previous chemotherapy (neoadj or adj) 64.4% and > 3 metastatic sites 21% of patients (19). The median cycles administered per pts was 7 (1-28) and the relative median dose intensity was 0.93 for B, 0.89 for P and 0.91 for G. Of the 76 pts with response assessment, the overall response rate obtained was 72% with a clinical benefit of 89.5% (80.3-95.34%). Of the 82 pts with a median follow up of 20.21m (0.23- 30.07), median PFS (50% events) for these pts was 11.51 m (9.01-17.6), the median duration of first response (MDR) was 12.4 m (7.6-15.2) and the median OS (42% events) was 27.4 m (21.9- NA). The one year OS % was 84.15 (74.27 – 90.47). Toxicity was generally manageable. Related AEs have been reported in 69/82 pts which were mostly mild or moderate. Safety analysis revealed 24 SAEs in 21 pts Conclusions: Bevacizumab in combination with paclitaxel and gemcitabine showed significant OS compared with the published data with paclitaxel and gemcitabine and high clinical benefit with manageable safety profile.
Patterns of docetaxel application in breast cancer patients from China: Experience in 42 cancer centers.
Authors: Xu Binghe ,   China TAX BC Group
Published: March 2020

e11537

Background: Docetaxel is considered as a fundamental drug in the treatment of breast cancer. It has been extensively incorporated into the neoadjuvant, adjuvant and metastatic treatment. The aim of this study was to investigate how breast cancer patients are treated with docetaxel in China. Methods: A retrospective review of chemotherapy with docetaxel performed from 2009 to 2011 was carried out in China. Study included all patients diagnosed with invasive breast cancer and treated with docetaxel-containing regimens in forty-two cancer centers from 12 provinces in China. Regimens were compared in different subgroups based on stage, subtype, and lymph node (LN) status. Patterns of chemotherapy were also compared to published guidelines. Results: Among 2188 breast cancer patients treated with docetaxel, 1881 (86.0%) were in adjuvant or/and neoadjuvant setting (including 91 in both settings). The mean age was 48.7 (range, 14-82). Compared with 288 patients using docetaxel as single agent therapy, more patients (86.8%) used docetaxel-containing combination regimens. The mean cycle administered and dose for every cycle was 4.8 and 73.0 mg/m2, respectively. Dose reduction and delay occurred in 409 (19.7%) patients mainly due to non-medical factors (10.9%) and hematologic toxicity (5.9%). TAC, TA, TC, TX, and AC-T regimens were given in 34.8%, 19.7%, 17.4%, 5.3%, and 2.2% of patients respectively. TAC was used more frequently in triple-negative breast cancer (TNBC) than other patients (43.0% vs. 32.7%, P=0.004). In the (neo)adjuvant setting, TAC regimen was used more frequently in LN-positive patients than LN-negative group (44.2% vs. 30.0%, P<0.001). Of 1682 patients in adjuvant setting, 729 (43.3%) were treated with triplet (TAC or AC-T). In 290 patients receiving neoadjuvant chemotherapy, only 94 (32.4%) used TAC and none used AC-T (P=0.013). Conclusions: Docetaxel was widely used in the treatment of breast cancer in China, especially in the (neo)adjuvant setting. TAC regimen was the most frequent option, especially in patients with TNBC or LN-positive BC. Although AC-T was also recommended in adjuvant setting by most guidelines, it was less commonly used compared to TAC regimen in China.
Effect of clinical and biological factors on pathologic complete response (pCR) after neoadjuvant chemotherapy for patients (pts) with early-stage breast cancer (BC).
Authors: Kouchner Pierre , Spano Jean-Philippe , Guillot Eugenie , Touboul Emmanuel , Renouvel Florence , Lauratet Betty , Genestie Catherine , Campion Loic , Khayat David , Classe jean Marc , Lefranc Jean-Pierre
Published: March 2020

e11551

Background: To evaluate predictive factors that impact pathologic complete response (pCR) after neoadjuvant chemotherapy (NC) for BC pts. The identification of such factors may improve pt selection for neoadjuvant therapy to maximize the likelihood of breast conservation surgery (BCS) Methods: A total of 279 pts treated with NC (anthracyclines and/or taxanes based chemotherapy) for BC were analyzed. Pathologic response was evaluated using Sataloff classification. Student’s test and Fisher’s test were used for statistical analysis; OS and DFS rates were estimated by Kaplan-Meier analysis and log rank test for outcome. Results: According to the TNM classification, 87.4% of pts had T2 /T3 tumors, and 45.9% of pts had a lymph node involvement before NC. HER-2 over expression was found in 23.5 % and 18.6 % of pts had triple negative tumors. Forty three (43%) of pts achieved a clinical complete response. BCS was performed in 44.8%. pCR was 26.4% in the breast primary tumor and 32.8% in the axillary nodes. Univariate analysis showed that the following variables at diagnosis were correlated with a pCR: T2 vs T3/T4 (P<0.001), ductal invasive carcinoma (P=0.001), high grade (p<0.007), high mitotic index (P<0.001), estrogen receptor (ER) negative tumors (p=0.001), progesterone receptor negative tumors (p=0.001), chemotherapy with taxanes (p=0.0026), trastuzumab therapy (p<0.001) and the number of chemotherapy cycles (p=0.002). In multivariate analysis, ER negative, high mitotic index and HER-2 overexpression were significantly associated with a pCR (P<0.01). Lymph node pCR was a significant prognostic factor with 5 year RFS and DFS (respectively p<0.001 and p=0.016). At a median follow-up of 53.4 months, OS and DFS at 5 years were 86.1% and 24.2% respectively. Conclusions: Our data support the hypothesis that ER negative, high mitotic index and HER2 overexpression significantly predicted pCR in pts receiving neoadjuvant therapy for early BC. These results may suggest using such factors before deciding neoadjuvant chemotherapy in order to increase eligibility for BCS.
Identification of novel variant of EML4-ALK fusion gene in NSCLC: Potential benefits of the RT-PCR method.
Authors: Maus Martin Karl Herbert , Stephens Craig , Zeger Gary , Grimminger Peter Philipp , Huang Eric ,   R&D Departement at Response Genetics Inc.
Published: March 2020

e12007

Background: The discovery of the transforming fusion gene of the anaplastic lymphoma kinase (ALK) with the echinoderm microtubule-associated protein like 4 (EML4) as an oncogene in 2007 has led to its validation as a clinical target in NSCLC patients in a short period of time. The inhibition of the anaplastic lymphoma receptor tyrosine kinase has demonstrated to prolong progression-free survival compared to the standard of care chemotherapy in patients with advanced NSCLC that are ALK positive. However, the clinical implications of the 15 different variants of the EML4-ALK transforming gene described so far are currently not defined. Here we present a novel variant of the EML4-ALK fusion gene which we named variant 3c. Methods: RNA extracted from formalin fixed paraffin embedded (FFPE) specimens from patients with advanced and metastatic NSCLC was amplified, using primers and probes designed to detect specific EML4-ALK fusion gene fragments. Gel electrophoresis showed a different band for the new variant 3c compared to the known bands of positive cell lines for variant 3a and 3b. These findings were further investigated by dye-terminator Sequencing and FISH. Results: The novel variant, detected in two NSCLC specimens, is longer than v3a and shorter than v3b, representing an 18 base pair insertion of intron 19 of ALK between exon 6 of EML4 and exon 20 of ALK. All of the two samples showed exactly the same sequencing result. One of the samples was negative for FISH break apart testing and the other one showed a positive result, defined by ≥ 15% split nuclei as indicative of an ALK rearrangement. Conclusions: Compared to FISH technology, RT-PCR enables the detection of different isoforms of the EML4-ALK transforming gene, which can be validated by sequencing. Only one out of two samples that were positive for the new variant by RT-PCR could be confirmed by FISH. The clinical significance of the different variants, notably to resistance and response to ALK-Inhibitors and the concordance and sensitivity of FISH and RT-PCR should be subject to further investigations.
Implementation of a community-based cervical cancer screening program using visual inspection with acetic acid and Lugol’s iodine in Kutch District, India.
Authors: Grover Surbhi , Ju Melody , Lin Lilie L. , Krishnan Shobha
Published: March 2020

e12009

Background: Visual inspection with acetic acid and Lugol’s iodine (VIA/VILI) is increasingly reframed as a bridge modality through which low resource countries can provide cervical cancer screening while waiting for the more effective HPV DNA tests to become affordable. Often the screening programs are organized by government bodies that lack the trust of the local communities and hence such programs suffer from poor participation. Here we aim to describe a locally-sustained VIA/VILI screening program in rural Kutch district in India directed by Kutch Mahlia Vikas Sangathan (KMVS), a local NGO committed to women empowerment. Methods: All capacity-building measures (funding, training, materials, and healthcare workers) were rooted in the local community. Heath workers were sent to Tata Memorial Cancer Center in Mumbai for training. NGO members held information sessions prior the screening camps educating women about the significance of screening. A three-visit screening model using VIA/VILI was implemented. At first visit, all women were consented and screened. VIA/VILI positive women returned for a second visit for biospy. Biopsy positive women then returned for a third visit to arrange for treatment. All the screening camps were conducted in community buildings such as schools with the collaboration of the village leaders. Results: Screening camps were set up in 17 villages in 2010-2011, screening a total of 832 married women upto the age of 50. There were 0 cervical intraepithelial neoplasia (CIN) positive lesions or invasive cancers found. None of the women were lost to follow-up. Conclusions: It is feasible to develop a community level screening program and to provide cancer prevention needs from within a community. Future directions include further evaluation of downstream protocols after VIA/VILI tests, increasing health worker diagnostic and treatment capacity, and determining positive recruitment factors in women attending screening camps. The KMVS screening program has been well-received and has been approached by several other NGO’s and training centers seeking to build similar community-based cervical cancer screening programs.
Menstrual status and lung cancer in female patients from the Spanish WORLD07 database.
Authors: Cantos Blanca , Majem Margarita , Garrido López Pilar , Vinolas Nuria , Isla Dolores , Garcia-Campelo M. Rosario , Catot Silvia , Lianes Pilar , Artal Angel , Bover Isabel , Terrasa Josefa , Blasco Ana , Rolfo Christian Diego , De Castro Javier , Gonzalez-Larriba Jose-Luis , Lazaro Quintela Martin , Izquierdo Angel , Vazquez Estévez Sergio , Figueroa Salvador , Felip Enriqueta ,   ICAPEM Association
Published: March 2020

e12012

Background: There is very little information about the menstrual status in women presenting with lung cancer. In other tumors, the menstrual status constitutes an independent prognostic factor. We proposed to investigate whether this status has any influence in clinical aspects, diagnosis or survival. Methods: WORLD07 is a Spanish prospective, multicenter, epidemiologic female-specific lung cancer database sponsored by ICAPEM, a professional association committed to WLC research. Results: Between October/2007 and October/2011, 1371 p newly diagnosed WLC were included in an e-database from 32 Spanish centers. Patient (p) characteristics were: median age 71.1 years (y)(range 22-91); median age of menarche 13y.; motherhood 91.2% (median 2.3 children, median age at first child 26.4y); oral contraceptive use 11.9%; postmenopausal 86% (median age of menopause 49y. No statistically significant differences were found with respect to menstrual status, clinical characteristics, histological type, nor in the TNM at diagnosis. Median overall survival in pre-menopause (preM) was 24.2 months (m) and 27.5 m in post-menopause (postM). Overall 1 year survival in both groups was similar, 70% IC95% (61.5-79.1%) in preM vs 72.4% IC 95% (69.15-75.7%) in postM, and at 2 years, was 50% in both. Conclusions: According to our e-database, the menstrual status does not have any significant influence in the presentation, histologic type or survival in women with lung cancer.