bluuebunny/crossref_metadata_2025 huggingface dataset:
Metronomic cyclophosphamide and capecitabine combined with lapatinib in heavily pretreated metastatic breast cancer (MBC) HER2-positive patients.
Authors: Cagossi Katia , Lazzaretti Maria Grazia , Ferrari Alessia , Razzini Giorgia , Leporati Meri , Silvestri Rosangela , Iadanza Manlio , Iop Aldo , Artioli Fabrizio
Published: March 2020

e11071

Background: Current therapeutic goals for MBC, as an incurable disease, are symptoms and prolonged disease control together with good quality of life. Metronomic chemotherapy has shown efficacy in patients with metastatic breast cancer. We evaluated the efficacy and tolerability of the combination of anti-angiogenetic activity of metronomic chemotherapy with a tyrosine kinase inhibitor such as lapatinib in heavily pre-treated MBC HER-2 positive patients. Methods: Metastatic breast cancer patients HER-2 positive with CEA or Ca15.3 elevated, measurable disease, prior systemic therapy (chemotherapy and/or hormonal therapy) for advanced disease, ECOG performance status < 1 and life expectancy longer than 3 months. MBC patients were treated with metronomic oral capecitabine (1500 mg daily) and cyclophosphamide (50 mg daily) plus lapatinib (1250 mg daily). The treatment was given until disease progression or unacceptable toxicity. Primary objective was time to progression (TTP) and safety. Results: Tenpatients were included. Median age was 56 years old (range 46-76). Median number of previous chemotherapy lines was 5 (range 2-10). Median time to tumor progression was 4 months (2-7). No complete response was observed. Six out of ten patients (60%) with pre-existing only bone metastases achieved a stable disease and/or partial response and are still on treatment after 6 month of therapy. At the same time 100% of these patients exhibited reduction of serum marker concentrations to normal range. No grade 3-4 toxicity was reported. There was no decline in cardiac function. Hematological and gastro-intestinal toxicity was well tolerated (G1-2). No reduction of dose was needed. Conclusions: The treatment appears to be an effective and less toxic option in heavily pretreated MBC patients. Of note is the observed activity in patients with exclusive bone metastases. Monitoring of CEA and Ca15.3 during the first two months of treatment appears to provide a sensitive and economical means of identifying those patients who are responding to the therapy. Therefore, the combination of lapatinib with metronomic chemotherapy should be explored in advance for osseous MBC.
Lapatinib efficacy according to metastatic sites in trastuzumab pretreated patients with HER2-positive metastatic breast cancer: An analysis form IntERB registry in the Czech Republic.
Authors: Grell Peter , Kandrnal Vit , Zbynek Bortlicek , Vyzula Rostislav
Published: March 2020

e11072

Background: Lapatinib is an oral dual tyrosin kinase inhibitor of EGFR and HER2 and compared to trastuzumab penetrates to CNS. We evaluated efficacy and safety of lapatinib treatment according to different metastatic sites involvement using data from IntERB registry that has been initiated and run by Czech Society for Oncology and Institute of Biostatistics and Analyses at Masaryk University, Brno, Czech Republic. Methods: An analysis included 213 patients with HER2 positive metastatic breast cancer treated from January 2007 to September 2011. Lapatinib was mostly administered orally 1250mg/day with capecitabine (2000mg/m2 D1-14), 16 patients received lapatinib in monotherapy. All patients had experienced progression during prior trastuzumab based therapy. Results: Median age was 56 years (range 23 – 78). Median duration of lapatinib therapy was 20.6 weeks (range 1–146). Complete response was achieved in 13 patients (6.1%), partial response in 31 (14.6%), stable disease in 118 (55.4%). In 26 disease have progressed (12.2%); response could not be assessed in 25 patients (11.7%). PFS for whole group was 7.1 months (95% CI 5.9-8.5). Overall survival was 17.2m (95% CI 15.8-18.6), probability of 6m OS was 80.3% and 1-year OS was 64%. Metastatic sites specific survival was evaluated in 103 patients. CNS dissemination was initially diagnosed in 31 patients (30.1%), PFS in this group was 6.2m (95% CI 3.3-9.1), OS was not reached, 6-m OS was 67.3%. In non-CNS group (skeletal metastasis in 49.5%, lung 38.8%, hepatic 36.9%, lymphatic 17.5%, other 15.5%) was PFS 6.3m (95% CI 1.6-11.1), OS 22.0m (95% CI 15.3-28.8) and 6-m OS was 88.2%. Most common toxicities were diarrhea in 11.7% patients, rash/skin toxicity in 10.8%, nausea/vomitus in 5.2% and hepatotoxicity in 2.3%. No cardiac toxicity was reported. Therapy was discontinued due toxicity in 9.0%. Conclusions: Lapatinib in combination with capecitabine proved its efficacy in trastuzumab pretreated HER2 positive metastatic breast cancer. Even in patients with CNS involvement was achieved a notable PFS and OS, comparable to non-CNS group of patients. Therapy was well tolerated.
Prognostic analysis according to the expression of hormone receptors in HER2-positive breast cancer.
Authors: Gallego Jimenez Inmaculada , Morales Pancorbo David , Fuentes Pradera Jose , Salvador Javier , Bayo Juan L. , Bernabé Reyes , Rodriguez de la Borbolla Maria , Fernandez Parra Eva , Lopez Ladron Amelia
Published: March 2020

e11075

Background: Overexpression HER 2 + + + is a distinct group within the breast cancer with different treatments in both the adjuvant and advanced setting. However, from the clinical point of view, there are significant differences within this group HER2 + + + referred to response to trastuzumab, metastatic sites and survival intervals. Recently reported data guides to a worse prognosis in the subgroup expressing hormone receptors. We propose to study these differences in HER2 + + + between subgroups hormone receptor positive and negative. Methods: Retrospective observational study of all patients diagnosed with HER2 + + + at the Hospital Virgen de Valme between the years 2005-2011. We studied the disease-free interval (DFS) and global survival (OS). We also studied the frequency of brain metastases and cerebral disease-free interval (BDFS). We explore differences between the hormone receptor-negative groups (group A) and positive (group B). All patients have been treated with at least one line of trastuzumab. Results: N = 73 (40 group A and 33 group B). Median age was 58 and 55 respectively. 33 patients had metastases in the course of the disease. 7 patients initially diagnosed with metastatic stage. There is a difference of 5.0 months in group A favorable DFS (p = 0.28). The OS was 52 months in group A versus 48 months in group B (difference of 4 months p = 0.18). The BDFS was 57 months for group A and 15 months for group B (p = 0.1). The incidence of brain metastases was 27% versus 9%. Conclusions: Our data suggests a better prognosis in terms of DFS, OS and BDFS in hormone receptor-negative group. Likewise, the incidence of brain metastases was three times lower. We need well design clinical trials, monitoring and therapeutic strategies for this subgroup of patients.
Population-based outcomes of patients (pt) with early-stage HER2-positive breast cancer treated with adjuvant trastuzumab (T).
Authors: Noonan Krista , McCarthy Joy S.
Published: March 2020

e11079

Background: Phase III trials have shown clinical efficacy of T when combined with chemotherapy in HER2-positive early stage breast cancer, decreasing recurrence by 50% and increasing survival by 30%. 15-20% of early stage breast cancers demonstrate amplification of the HER2 gene, which is associated with a poor prognosis. The aims of this study were to evaluate the clinical effectiveness of T, and explore potential prognostic factors. Methods: Pts with stage I-III breast cancer overexpressing HER2 from 2005 to 2010, assessed in Newfoundland and Labrador’s cancer centre were retrospectively identified from the Provincial Tumour Registry. Pt, treatment, and tumour characteristics were extracted. Kaplan-Meier curves were used for survival analysis, and Cox Proportional Hazards Models were used to identify prognostic factors and evaluate their impact on outcomes. Results: A total of 148 pts were identified. The median age was 56 years, and 76% received T. At a median follow-up of 25 months, overall survival (OS) was 97% (p=0.0002), and disease-free survival was 96% (p<0.00) for pts receiving T. Younger age, smaller tumour size, and lymph node negativity were favorable prognostic factors. There was an 83% decrease in risk of breast cancer recurrence in the patients receiving T. Discontinuation of T occurred in 6.2% of patients due to a decreased ejection fraction. Conclusions: This population-based analysis demonstrates T’s favorable impact on 25-month DFS, OS, and safety. This adds to the body of literature, showing clinical effectiveness and tolerability of T. [Table: see text]
Role of lapatinib in metastatic carcinoma breast.
Authors: Behera Manoj Kumar , Julka Pramod Kumar , Rath Goura Kishore
Published: March 2020

e11082

Background: Metastatic breast cancer (MBC)is the leading cause of cancer death among women. Lapatinib is a small-molecule TKI that constitutes an alternative in HER2 intracellular signaling pathway blockade, with no cross resistance with Trastuzumab. The combination of Lapatinib and Capecitabine in women with HER2+ advanced breast cancer that progressed following treatment with anthracycline, taxanes and trastuzumab is superior to single agent therapy with Capecitabine. Methods: In this study conducted from March 2010 to June 2011, a total of 30 patients with progressive HER2+ MBC following therapy with at least anthracycline, taxanes and Trastuzumab and then receiving Capecitabine@2gm/m2/day for D1-14, 3 weekly with Lapatinib@1250mgm/day, daily were analyzed. Palliative RT of 8Gy/1# was delivered to the involved bones, and WBRT of 30Gy/10#/2 weeks was delivered to the patients with brain metastasis before starting this combination oral chemotherapy. Results: The median age at primary diagnosis was 45 years. 18 patients were ER and/or PR +. Most common site of metastasis was bone (50%) and brain (23%). 30% of patients had multiple sites of metastasis. All the patients of stage III-IV had received NACT for 3 cycles at least. 80% patients had received adjuvant chemotherapy according to the aggressiveness of the disease before/after loco regional RT. 68% patients also received adjuvant Trastuzumab. With a median follow up of 4 months of treatment with Lapatinib with Capeciatbine, the overall response rate achieved was 75% with only 3 patients of solitary lung and liver metastasis showed CR. 40% patients had PR and 33% had stable disease and rest of the patients progressed. Bony symptoms were better controlled with palliative RT and it was seen that pain control was much better in those patients who received this combination. The TTP ranged from 2 to 6 months. All the patients tolerated well except 4 patients who presented with Gr III diarrhea, responded with Capeciatbine dose reduction by 20%. Conclusions: It is evident from this study that this combination regimen of Lapatinib and Capecitabine is effective and well tolerated in patients of HER2 + MBC. Further larger studies are required to confirm the significance of this regimen in our set up.
Concomitant chemoradiotherapy in women with stage II-III breast cancer.
Authors: Richardet Eduardo arnoldo , Laura Perelli , Richardet Martin Eduardo , Castagneris Nicolas , Cortes Matias Nicolas , Molina Matias
Published: March 2020

e11501

Background: To demonstrate the compliance of radiotherapy and chemotherapy with concomitant taxanes by avoiding delays initiation of that treatment Methods: Retrospective, observational, and descriptive. We analyzed the medical records of 50 patients from June 2006 to December 2010 with an average follow up of 27.26 months (9 months to 56 months), in which all completed conservative surgery. The chemotherapy used was AC x 4 cycles (doxorubicin 60 mg/m2, Cyclophosphamide 600 mg/m2 on day 1 every 21 days) followed by weekly paclitaxel 80 mg/m2 for twelve weeks, concomitant with radiation in the affected breast. Standardized treatment was indicated to patients with positive hormone receptors. Results: Patients`s age averaged 53.58 years (33 years and 74 years) All patients received the planned chemotherapy, with a delay of 63.24 days, from the surgery to the first cycle of chemotherapy (20 days to 110 days. The radiation treatment was initiated in 143.4 days (90 to 205 days) on average after the surgical treatment.It was reported that 8% (n = 4) discontinued the treatment due to the toxicity of the radiation therapy: actinic dermatitis grade 3 and 4. The average number of days without radiation therapy due to toxicity was 6 days (3 to 9 days).With respect to chemotherapy, 22% (11) interrupted it because of hematologic toxicities (neutropenia, thrombocytopenia), constitutional toxicities (fatigue) and arthralgias. Regarding chemotherapy, the average time without treatment was 18 days (1 to 4 cycles).There were no cardiac or lung related adverse events. All other toxicities were well tolerated with concomitant medication. Conclusions: In our population, it is possible to carry out concomitant chemo-radiotherapy with acceptable early toxicities and compliance in patients with breast cancer.
Correlate effects of local therapy for the primary tumor in metastatic breast cancer at diagnosis with molecular subtypes.
Authors: Hijri Fatima Zahra , Arifi Samia , Brahmi Sami Aziz , Bouyahia Nezar , Benbrahim Zineb , Daoudi Khaoula , Najdi Adil , Berreho Mohamed Amine , Nejjari Chakib , Amarti Affaf , Nawfel Mellas , El Mesbahi Omar
Published: March 2020

e11502

Background: Few studies demonstrated that surgical resection of the primary tumor in patients with metastatic breast cancer at diagnosis is associated with significant improvement of survival. The aim of this study is to evaluate the correlation impact of local surgery in metastatic breast cancer at diagnosis with molecular subtypes. Methods: A retrospective study was conducted from 2007 to 2011 in our institution, of all stage IV breast cancer patients; who undergo breast surgery. Clinical , tumor characteristics, molecular subtypes, prognostic factors, therapeutic results data were analyzed. Results: We selected 59 cases. The mean age was 36 years (range: 22-44). 55 % women presented with locally advanced breast cancer with 13% T4 d . All patients underwent mastectomy except 4 who underwent conservative surgery .41 patients had axillary lymph node dissection. 63% were luminal A, 17% were luminal B, 7% were Her2-positive and 13% were basal-like . All patients received anthracycline based regimen and only 33% received taxanes. Loco regional radiotherapy (RT) was given to 6 women. Average follow-up was 13 months: - 20 patients represented partial response : 15 patients in luminal A , 3 patients in luminal B ,1 patients in basal-like and 1 patient in HER2-positive. - 11 patients (19%) were stable : 9 patients in luminal A and 2 patient in luminal B . -24 patients represented a progressive disease including 11 patients presented locoregional recurrence : 75 % in HER-positive, 40 % in basal-like, 50% in luminal B and 30% in luminal A (p=0.4). - 4 patients died in basal-like. The median local recurrence-free survival was 19 months and the median progression-free survival was 20 months. The local relapse is less observed in patients who: have a small tumor size (p = 0.003), had axillary lymph node dissection (p = 0.02) and loco regional radiotherapy (p = 0.03). The metastatic progression is less observed in patients with small tumor size (p = 0.01). Conclusions: Local Therapy of the primary tumor improves local control of disease, particularly in women with Small tumors. However, no significant correlation between impact of locale therapy and Molecular Subtypes was observed.
Correlation of target motion with the dosimetric variance on breast and OAR during whole breast radiotherapy with 4D-CT.
Authors: Li Jianbin , Wang Wei
Published: March 2020

e11521

Background: To explore the correlation between the respiration-induced target motion and volume variation with the dosimetric variance on breast and OAR during free breathing. Methods: Seventeen patients after breast conserving surgery underwent respiration-synchronized 4DCT simulation scans during free breathing. The treatment planning constructed using the end inspiration (EI) scan, then copied and applied to the other respiratory phases and the dose distribution was calculated separately. To evaluate the dose–volume histograms parameters for the PTV, ipsilateral lung and heart. Results: During free breathing, the CTV motion vector was 2.09 ± 0.74 mm, and the volume variation was 3.05 ± 0.94%. There was no correlation between the volume variation of CTV and target/OAR dosimetric variation (|r| = 0.39 ~ 0.48). In anteroposterior (AP), superoinferior (SI) and vector directions,the CTV movement correlated well with the mean PTV dose, conformal index (CI), and the lung volume receiving high dose (V20, V30, V40, and V50) (|r| = 0.651 ~ 0.975); in SI and vector directions, the CTV displacement only correlated with the heart volume receiving >5Gy (V5) (r = -0.795, 0.687). The lung volume variation and the lung volume receiving high dose correlated reasonably well (r = 0.655 ~ 0.882), and the correlation only exist between the heat volume variation and the V5 of heart (r = -0.701). Conclusions: Target movement correlated well with the target/OAR dosimetric variation in certain directions, indicating that whole breast IMRT assisted with breathing control or respiratory-adapted gated treatment will promote the accuracy of dose delivery during radiotherapy. To minimize lung irradiation, gated treatment maybe most precise if centered at end expiration.
Dream content and sleep changes in women after mastectomy.
Authors: Cicolin Alessandro , Airoldi Mario , Giordano Alessandra , Francese Valentina , Peila Elena , Tribolo Antonella , Pedani Fulvia , Torta Riccardo
Published: March 2020

e11524

Background: The concerns people express in their dreams are the concerns they have in waking life (Domhoff – Dreaming 11: 13-33; 2001) . In this abstract we report in breast cancer patients (BCP) the dream content, sleep quality and quantity , and their mood both before and after mastectomy (M), to determine whether a loss of a body part could change body schema and actuate a sexual sphere restructuring. Methods: Consecutive menopausal BCP without impaired cognitive impairment (MMSE < 24), without psychiatric and/or sleep disorders, not assuming drug that could affect REM sleep and waiting for M were enrolled. Pts were evaluated at T0 (7-10 days before M) and at T1 (3 months after M) with: 1) Dream Report Form (DRF – Domhoff , 1996) in which pts describe 5 recent dreams; 2) Dream Remind Questionnaire (DRQ) to obtain explicit content of dreams; 3) Beck Depression Inventory (BDI); 4) State Trait Anxiety Inventory , Form Y(STAI-Y). Results: Thirty pts were eligible: 15 pts dropped out (withdrew consent between T0 and T1); 15 pts completed the study (mean age = 51 yrs , range 45-66 yrs; education = 10 +/- 4 yrs). After M the total sleep time was significantly increased ( p<.05) ; sleep quality was unchanged .STAI and BDI were not significantly different. . At T1 we found a statistically significant increase in stated presence of wise self, determined self, curiosity, anger and shame. Excitement was reduced in T1.At T1 there is a reduction of violent and erotic environments, frightened-self perceptions, and repulsions, along with a slight increase of loved and powerful self-perception. In T1 dreams we found an increased presence of males and family characters, the proportion of dead people, striving elements with failure, a decreased presence of friends and aggressiveness. Torso-anatomy was significantly different in T1. Conclusions: Our results confirm a continuity between dreams and waking life. Dream content modifications are specifically related to body image.
Prognostic value of Bcl-2 in breast cancer.
Authors: Ibeas Patricia , Lopez-Gonzalez Ana , Doger de Speville Bernard Gaston , Huelves Miriam , Lopez Roberto , Almagro Elena , Palka Magda , Ruiz-Valdepeñas Andrea , Perez Callejo David , Provencio Mariano
Published: March 2020

e11527

Background: Breast cancer is a heterogeneous disease with prognostic factors used by the oncologists to decide the treatment. Bcl2 is an antiapoptotic proto-oncogen involved in DNA break process that has been defined historically as a poor prognostic factor. This study was conducted to confirm whether or not bcl-2 is an independent prognostic factor. Methods: In this study, we have reviewed all patients who were diagnosed at our hospital between January 2007 and December 2008 (99 patients). Inclusion criteria were patients diagnosed of breast cancer whose anatomopathological report showed bcl-2 status as well as the rest of the parameters measured. The parameters measured were age, past medical history, menopausal status, TNM, hormone receptors, HER2, p53, Ki67, bcl-2, treatment applied, date of relapse (if any), date of death ( if occurred). All of them characterized by centralization measures. We conducted an analysis of prognostic factor that influenced survival. Results: The average age of diagnosis is 54.6 years (30-94 years). 42.4% were premenopausal. The average tumor size was 2.59 cm ( 0.5-7.5 cm). 81.8% had positive estrogen receptors. 92% were HER2 negative by inmunohistochemistry. 62.6% were p53 negative. Bcl-2 was 84.8% positive. The distribution by stage at diagnosis was: stage I 26.3%; stage II 49.5%; stage III 22.2%. Disease free survival for patients bcl2(+) was 45.6 months versus 22.6 months for patients bcl2 (-) (0.12-22.2; p: 0.00125). Overall survival for the group bcl2(+) was 48 months (41.6-54.3) and bcl2 (-) was 48.24 months (42.48 to 54). Conclusions: We can state that bcl2 is not an independent prognostic factor. Despite the value in other diseases, the determination of bcl-2 by inmunohistochemistry in breast cancer in stages I, II and III at the moment of the diagnosis does not provide any prognostic information.
Results of a phase II study of capecitabine-based doublets in the treatment of metastatic triple-negative breast cancer (mTNBC).
Authors: Fan Ying , Xu Binghe , Liao Yuqian , Ma Fei , Yuan Peng , Wang Jiayu , Zhang Pin , Li Qing , Xuan Lixue , Luo Yang , Ding Xiaoyan
Published: March 2020

e11538

Background: It is extremely important to identify proper cytotoxic agents for TNBC which had limited choices except chemotherapy. Capecitabine are well established as a major chemotherapeutic agent in metastatic setting. The efficacy of capecitabine-based chemotherapy has not been prospectively studied in TNBC and data remains scant. This study was designed to investigate the efficacy of capecitabine-based doublets in the treatment of metastatic TNBC. Methods: Eligible metastatic TNBC women with measurable diseases were recruited to receive either TX regimen (docetaxel 75mg/m2 iv d1 plus capecitabine 1000mg/m2 bid, d1-14,q3w) or NX regimen (vinorelbine 25mg/m2 iv d1, 8 plus capecitabine 1000mg/m2 bid, d1-14, q3w) at the discretion of physicians for up to 6 cycles, until disease progression or unacceptable toxicity. The primary endpoint was objective response rate and secondary endpoints included progression free survival (PFS), overall survival (OS). Results: 45 mTNBC patients, 27 in TX and 18 in NX were recruited, mostly (73.3%) as 1st line and the remaining as the 2nd line. The total objective response rate was 20.0% and clinical benefit rate was 62.2%. After a median follow-up of 28 months, PFS was 5.2 months (95%CI, 4.1-6.3mons) and OS was 18.2months (95%CI, 8.7-27.7mons). Almost half of the patients (22/45) progressed during treatment or within one month of the treatment discontinuation. PFS was significantly longer if patients got CR/PR (9.6 vs 4.3mons, P=0.015). When comparing two doublets, the response rate was numerically but not statistically lower in TX group than in NX group (14.8% vs 27.8%, P=0.449). Similarly, no difference was found in either PFS (4.9 vs 5.2 mons, P=0.483) or OS (21.5 vs 18.3 mons, P=0.964) between two regimens. Conclusions: Although the overall survival seems to be reasonable, efficacy of capecitabine-contained TX or NX regimen was relatively poor in terms of tumor remission and progression free survival in mTNBC patients, suggesting capecitabine may have limited potency in this subtype. These two combinations may be considered to be acceptable but may not be recommended as prior choice for mTNBC patients.
Compartmentalization of tumor cells to the CSF or peripheral blood of a breast cancer patient with CNS metastasis.
Authors: Allen Joshua , Patel Akshal , Dicker David , Sheehan Jonas , Glantz Michael J. , El-Deiry Wafik
Published: March 2020

e11544

Background: We recently adapted the CellSearch system to detect cerebrospinal fluid tumor cells (CSFTCs) in breast cancer patients with CNS metastases and found that the CSFTCs correlate with disease burden. Here, we present the enumeration of CSFTCs and peripheral blood tumor cells (PBTCs) in a patient with metastatic breast cancer during treatment with intrathecal (IT) chemotherapy. Methods: We enumerated CSFTCs and PBTCs in a patient with ER+, Her2-, BRCA2+ breast cancer and CNS metastases who received IT chemotherapy and systemic chemoradiation. The patient was initially diagnosed with locally advanced breast cancer and underwent bilateral mastectomies followed by AC-T one year prior to CNS relapse. Tumor cell enumeration was conducted every 1-2 weeks from 7.5mL of peripheral blood or 9mL of CSF along with CSF cytology, Karnofsky performance status (KPS), neurologic examination and radiographic studies during the IT chemotherapy and subsequent systemic chemoradiation. Results: At the beginning of the IT chemotherapy the patient presented with diplopia, gait ataxia, 7th facial nerve palsy, confusion, and intractable headaches, an initial burden of 19570 CSFTCs and 10-45 PBTCs, a KPS of 80, and no systemic disease. Tumor cell counts dropped rapidly in response to IT therapy alone to 0-1 CSFTCs and 3 PBTCs, all neurologic symptoms resolved, and the KPS increased to 90. The patient subsequently suffered progression of systemic disease with development of bone and brachial plexus metastases. PBTCs rose from 3 to 64 during this same period, whereas CSFTCs remained at 0-1. The CA 27-29 level increased from 111 to 214. CSF cytology and neuro-radiographic imaging cleared in the face of progressive systemic disease. Conclusions: There was a compartmentalization of metastatic tumor cells to either the blood or the CSF in this patient. We hypothesize that tumor cells in the CSF or peripheral blood migrate to the untreated compartment during compartmentalized therapy, resulting in disease recurrence in the untreated compartment. Preliminary data on other patients supports this hypothesis, which may represent an important mechanism for disease recurrence in patients with potentially curable disease.
Analysis of pattern, time, and risk factors influencing recurrence in triple-negative breast cancer patients.
Authors: Niwinska Anna , Pogoda Katarzyna , Murawska Magdalena , Pienkowski Tadeusz
Published: March 2020

e11553

Background: The aim of the study was to assess the rate, pattern and time of recurrence in patients with triple-negative breast cancer (TNBC) treated in one institution. The second goal was to evaluate factors influencing recurrence and overall survival in this group of patients. Methods: 2534 consecutive breast cancer patients were diagnosed at the Cancer Center and Institute of Oncology in Warsaw, Poland, between January 2005 and December 2006. Out of 2534 patients, 228 (9%) were TNBC (ER/PR/HER2-negative). The clinicopathological characteristics were determined using descriptive statistics. The overall survival (OS) and disease-free survival (DFS) were calculated using the Kaplan-Meier method. The univariate and multivariate analyses were developed to identify factors influencing recurrence and survival in TNBC patients. Results: Most of the patients were diagnosed with stage II or III breast cancer (47% and 34%, respectively), the median age at diagnosis was 54.5 years. The most common histological type was ductal cancer (81%). 31% of patients were treated with neoadjuvant chemotherapy and 49% with adjuvant chemotherapy – almost all consisted of anthracyclines. 6 years of observation revealed that the metastatic disease occurred in 35% of all TNBC patients: 15% in the brain, 14% in the lungs, 11% in the bones, 8% in the liver and 14% had locoregional relapse. The highest risk of recurrence was during the first 3 years after primary treatment and then during the next two years of observation it did not change. Median DFS and OS were not reached at the time of analysis, 6-year DFS and OS were 68% and 62%, respectively.Factors influencing recurrence were: tumor size and systemic adjuvant chemotherapy while factors influencing overall survival were: tumor size, nodal status, adjuvant/neoadjuvant treatment and metastases in the brain, liver and bones. Conclusions: Characteristic pattern of recurrence in time was revealed. The tumor size was responsible for recurrence despite lack of involvement of lymph nodes. Aggressive adjuvant/neoadjuvant treatment ordered in all clinical stages of TNBC (including N0) was factor responsible for avoiding local and distant relapse and prolonging overall survival.
Planning the boost in early-stage breast carcinoma: Comparison of two methods.
Authors: Krakobsky Vanesa
Published: March 2020

e11555

Background: When it comes to breast-conserving surgery the boost volume becomes a critical target: it has the highest risk of residual cancer cells. Failing this target may impact local recurrence outcomes. At our institution the most common methods to contour the tumor bed are: the scar-based planning guided by fluoroscopy (2DP) and the one that relies on the visualization of the seroma under CT (3DP). Since clips are not routinely used the boost demarcation becomes challenging. We evaluated the accuracy of the breast boost volume treated with 2DP compared with 3DP. Additionally we evaluated whether or not the lumpectomy scar is a suitable landmark to define the tumor bed. Methods: 20 patients diagnosed with breast cancer stage I-IIA underwent tumor bed boost planning using two techniques: 2DP and 3DP. CTV prescription dose: 16.2 Gy, 1.8 Gy/d. All the information concerning to the 2DP was reproduced in a radiotherapy planning system. Statistical analysis: match pair t-test and coefficient of variation were used to test for an association among the two planning techniques for tumor bed coverage. D95, D90, V15, volume, medium lung dose (MLD) and geographic miss (GM) were analyzed. Pearson correlation analysis was used to assess the relationship between CVS, date of surgery, age and previous chemotherapy. Other items taken into account were the match between the scar and the seroma and how good the visualization of the seroma was by using the CVS. Results: 2DP was inaccurate: the mean D95, D90 and V15 were 3.12 Gy, 4.6 Gy and 29% respectively (variation coefficient: 135%, 107% and 65% respectively) The mean D95, D90 and V15 for the 3DP were 14.34 Gy, 15 Gy and 88% respectively (variation coefficient: 6%, 3% and 7% respectively). The difference between the mean 2DP D95 and 3DP D95 was 11 Gy (95% CI, 9 Gy to 13 Gy, p< 0.001). Percentage of GM was: 80% (95% CI, 63% to 97%). All the seromas were finely visualized There was no correlation between CVS, age, prior chemotherapy and date of surgery. Larger volumes and MLD 3DP: 373.1 cm3 vs. 248.8 cm3 and 0.27Gy vs. 0.14 Gy respectively. Only 45% of the lumpectomy scars matched the seroma. Conclusions: CT-based planning allows for optimal tumor bed coverage. The lumpectomy scar is often a poor indicator of the tumor bed.
Accurate excision of nonpalpable breast lesions with the new device system.
Authors: Luo Zhongyao
Published: March 2020

e11557

Background: A histological diagnosis for nonpalpable breast lesions (NPBL) is required to determine suitable therapy. The open-breast biopsy (OBB) is the gold standard to determine the nature of NPBL. However, it is not easy to accurately remove whole breast lesions due to insufficient safe margin of lesions excised. To improve accuracy for removal of NPBL, we designed new tools to assist surgeons to accurately localize and remove NPBL during OBB. Methods: The new device system has two primary parts. First is a set of accurate-resection devices composed of a rotary cutter, a pair of inner and outer tubes, two pairs of concave and convex curved hooks, and a curved incision plate. The second part is the 12 o'clock localization method used to accurately position lesions three-dimensionally after the breast tissue is excised cylindrically. Thus, the exact location of breast lesions removed can be precisely traced back to the original breast tissue location. Results: 100 patients with a total of 149 OBB were studied using the new device system guided with needle localization under ultrasound. 112 out of 149 procedures were identified as nodule. Among 112 cases, 95 were breast fibroadenomas, 10 were mammary adenosis with a trend to form fibroadenoma, 5 were mammary adenosis, and 2 were adipomas. The remaining 37 cases possessed clusters of calcified lesions with small nodule. 32 were benign lesions with calcinosis, and the other 5 lesions were identified as breast cancer. Pathological examination demonstrated that 144 NPBL were accurately resected with accurate-resection devices. However, 19 out of 144 breast lesions were not completely removed the first time. Thus the second surgical procedure was performed for the 19 cases based on 12 o'clock localization method. The results demonstrated that the remaining lesions were accurately and completely eliminated with the second procedure. All patients were followed up with for 2 to 48 months post procedures. These patients treated with accurate resection devices were very satisfied with no breast deformation. Conclusions: The new device system is easy to use and has very low cost. It is very comfortable for the patient and is of great help in accurately localizing and resecting the lesions to the surgeon.
Expression of stathmin in tumor to predict response to neoadjuvant chemotherapy with docetaxel-containing regimens in locally advanced breast cancer.
Authors: Meng Xuli
Published: March 2020

e11566

Background: We performed this retrospective study to evaluate the value of clinicopathological factors and a novel molecular marker stathmin in predicting treatment response to neoadjuvant chemotherapy (NCT) with docetaxel-containing regimens in patients with locally advanced breast cancer. Methods: Fifty-four consecutive locally advanced patients receiving docetaxel-containing NCT between January 2006 and July 2010 in Zhejiang Cancer Hospital were included. The expression levels of estrogen receptor (ER), progesterone receptor (PR), epidermal growth factor receptor-2 (HER-2), and p53 were detected by immunohistochemistry, while expression of stathmin mRNA was measured by Quanti-Gene assay. Results: The overall clinical objective response (cOR) rate was 75.9% (41/54) in breast. A total of 34 patients (63.0%) experienced pathological OR (pOR), with pathological complete remission (pCR) rate of 20.4% (11/54) in breast and 16.7% (9/54) in both breast and axilla. In univariate analysis, there were associations of pOR in both breast and axilla with age (P=0.054), ER status (P=0.059), subtypes (P=0.062), p53 (P=0.030), and stathmin expression (three terciles) (P=0.039). Mean expression of stathmin in pOR group was 0.410, compared with that in no response group of 0.556 (P=0.051 by Student’s t-test). Similarly, a lower expression of stathmin might represent a higher pCR rate (P=0.061). Moreover, the LOWESS smoothing plot showed the same trend, i.e., that tumor with a lower level of stathmin expression had a higher probability of response to docetaxel-containing NCT. After multivariate adjustment, both ER and stathmin kept being significant with hazard ratio of 4.58 (95% CI: 1.11-18.94, P=0.036) and 2.94 (95% CI: 1.26-6.86, P=0.012), respectively. Conclusions: ER and stathmin were independent predictive factors for NCT with docetaxel-containing regimens.
Population survey to assess the knowledge of smoking habit and its consequences on women (w) in Spain.
Authors: Majem Margarita , Artal Angel , De Castro Javier , Felip Enriqueta , Garrido Lopez Pilar , Isla Dolores , Bujosa Juan Ramon , Cajal Rosana , Vinolas Nuria
Published: March 2020

e12000

Background: Lung cancer (LC) w has reached epidemic proportions with a 600% increase in w’s death rate for LC. LC is the leading cause of cancer death in w in USA and the second in Spain. However, Spanish population is not aware of the significant increase in smoking and LC incidence in w. We performed a population survey to know the smokers’ characteristics and to assess the knowledge about smoking and its consequences especially in w. Methods: We conducted 1000 telephone interviews in Spanish population >18 years (y). Sample was distributed in proportion to the population by region with age and gender quotas: 48% were men (m), 52% w. Age distribution: 18-29y 16%; 30-44y 30%; 45-64y 32%; > 65y 22%. Results: The 17% and 25% of w were current and former smokers, respectively. The 27% and 38% of m were current and former smokers, respectively. People of 18-29y were the most current smokers (26%), and w smokers rate was higher than m. The 58% of w and 52% of m started smoking between 14-18y. Among students, 43% of w and 23% of m smoke. The 70% of smokers of 30-44y have tried to quit smoking, and having a relative with LC increased by 47% the possibility of quitting smoking as a young. Only 1/10 people had ever asked for their own LC risk, even if they had ever smoked or had a relative with LC. LC was the first disease named as smoking-related disease (58%). The 78% believed that nowadays more w smoke. The 60% believed that LC in w is increasing. Additionally, >40% belief that >75% of w LC have ever smoked. The 24% believed that tobacco hurts w more than m and the 55% that LC affects w more or equal than m. The 65% believed that breast cancer is the leading cause of cancer death in w in Spain and 13% that it is LC. 9/10 is aware about direct relation between tobacco and LC and the 50% believed that >50% of smokers will develop LC. The 97% believed that never smokers might also develop LC. Conclusions: Although the relation between tobacco and LC is overestimated, the 17% of w and 27% of m smoke. A large % of surveyed is aware that nowadays more w smoke, although only the 60% believed that LC in w is increasing. The highest rate of smoker w are those of 18-29y, especially among students, and >50% started smoking between 14-18y. Anti-tobacco campaigns are needed especially those targeting young w.
Smoking and prostate cancer risk in young men in Appalachian Kentucky.
Authors: Gowdar Indraneel , Mallikarjun Priya , Reddy Indraneel , Shankar Anjali , Dignan Mark
Published: March 2020

e12004

Background: Kentucky has the highest smoking rates in the US, with 25.2% of the adult population considered current smokers compared to 18.4% nationwide (CRC, 2011 statistics), as well as high rates of chronic conditions including diabetes, heart disease, and lung cancer. In particular, the Appalachian area of Kentucky appears to have particularly high rates of both smoking and prostate cancer, beyond what is typical for the state as a whole. Recent data on prostate cancer from the Kentucky State Cancer Registry from 2004-2008 showed an incidence rate of 144 vs. 139.8 per 100,000 for "Appalachia" and Kentucky as a state, respectively. The purpose of this study is to investigate the relationship between smoking and risk of prostate cancer in Appalachian Kentucky. Methods: Data were collected on all prostate cancers diagnosed from 1996-2005 in a large hospital serving the Appalachian region. Data were collected without identifiers. Relevant statistics recorded included age at diagnosis, family history, and smoking status (classified as current smoker, non-smoker, or unknown smoking status). Results: A total of 286 patients with diagnosed prostate cancer were collected. The patients ranged from 45 to 94 years of age at diagnosis (Mean = 71, SD = 9.8). Of the 286, 89 (31.1%) had never smoked, and 94 (32.9%) were current or former cigarette smokers (Mean pack years = 25.4). To control for the age-related increase in cancer risk, patients were separated into two age groups: age 65 and younger (n=86, 30.1%), and older than 65 (n=200, 69.9%). The proportion of the younger group who smoked was significantly greater than that of the older group (44.2% vs. 28%, respectively; p= 0.009, Fischer's exact test). Conclusions: These data suggest that smoking in males younger than 65 is positively associated with an increased risk of prostate cancer in Appalachian Kentucky. Further study is needed to elucidate this relationship, as well as to evaluate any association between smoking severity and Gleason score.
Relationship of testicular cancer incidence and cellular phone use.
Authors: Somer Robert A. , Surapaneni Rakesh , Beach Douglas Francis
Published: March 2020

e12008

Background: Because of the ubiquitous usage of cellphones, any health consequences, if found, would be of paramount importance. Many have questioned the relationship of cellphone radiofrequency waves and malignancies such as brain tumors. Because men usually store their phones in close proximately to the testicles, we analyzed the relationship between cell phone usage and testicular cancer. Methods: Testicular cancer data was obtained from SEER-9 United States Population Data Base of the National Cancer Institute. Cell phone subscription data was obtained from the World Health Organization publication. Initial data analysis was done from 1991 to 2008, with subsequent age specific and other analyses performed from 1999 to 2008. Trends over time were calculated as Annual Percentage Change of incidence rates (APC) by using log linear models. Results: Rates of United States mobile subscriptions increased exponentially since the late 1990’s reaching 88.87 percent of the population by 2008. There was no statistically significant change in incidence rates of all testicular tumors (APC 0.7; CI -0.2, 0.7), Seminoma (APC 0.2; CI 0.8, 1.1) and non-Seminoma (APC 1.4; CI -0.6, 3.4) from 1999 to 2008. In the age specific analysis, three groups showed an increase in incidence rates: all testicular cancer age 25-34 (APC 2; CI 0.6, 3.4), All testicular cancer age greater than 45 (APC 1.7; CI 0.1, 3.3) and Seminoma age 25-34 (APC 2.1; CI 0.6, 3.7). All these changes were only minor percentage increase when compared to mobile subscriptions. Conclusions: Based on incidence data, there is no convincing evidence of increased risk of testicular cancer from cell phone use. Given possible lag time incidence, continued monitoring is needed.
Higher prevalence of BRCA2 mutations among Chinese breast cancer patients in a community oncology clinic.
Authors: Keung Yi-Kong , Hu Adriana , Yeung Annie , Chan Amy , Hu Eddie
Published: March 2020

e12017

Background: According to a large US population-based study, BRCA1 and 2 mutations occur in about 6 and 4% breast cancer cases age <45. Asians have the lowest prevalence of BRCA1 mutation among five US racial groups. The prevalence of BRCA1 and BRCA2 mutations was reported as 8.1% and 2.7% among pts with family history in Shanghai, compared to 4.9% and 7.5% respectively in Hong Kong. We would like to explore the BRCA mutations in a clinic located in an Asian-majority community in California. Methods: Consecutive female breast cancer pts selected for BRCA testing according to NCCN guidelines are retrospectively studied from 10/2009 to 10/2011. Sequencing of all translated exons and immediately adjacent intronic regions of the BRCA1 and BRCA2 was performed on the peripheral blood (Myriad, Utah). Results: Twenty-six pts were included in this study. Six pts have bilateral breast cancers; 2 synchronous and 4 metachronous with intervals of 11-13 years. Nine pts (34.6%) had BRCA2 germline mutations, of which 5 were considered deleterious and 4 of uncertain significance. Eleven pts (42.3%) had no BRCA mutation. BRCA results were unavailable in six pts because they were either not yet done or denied by health insurance. Conclusions: 1. High prevalence of BRCA2 mutation is seen in our pts selected according to NCCN guidelines. The presence of BRCA2 but not BRCA1 mutation in our study is intriguing. 2. Triple negative breast cancer is not more prevalent in BRCA2 mutation carriers. 3. Similar frequency of family history of breast/ovarian cancer is noted among pts with or without BRCA2 mutation, deleterious or of uncertain significance. The role of the BRCA2 mutation of uncertain significance needs to be further elucidated. 4. Due to the small sample size, further study is required to confirm our findings. [Table: see text]
Malignant solid neoplasms in a population of immunosuppressed patients.
Authors: De Souza Caio Silverio , Simon Sergio D. , Melo Mendes Ana Valeria , Torralvo Helena Fragata , Ziviani Luciene Fabres , Villasboas Tercia Reis , Neif Joao Antonio Junior , Miranda Raelson Rodrigues
Published: March 2020

e12021

Background: Immunosuppression, whether caused by chronic use of immunosuppressive agents in solid organ transplant or by infection with human immunodeficiency virus (HIV), increases the risk of developing malignancies compared with the general population. This study aims to describe the profile of solid malignancies in immunosuppressed patients followed at the oncology clinic of the Federal University of São Paulo. Methods: Data were collected directly from the medical records of immunosuppressed patients followed in the Department of Clinical Oncology HSP / UNIFESP from January 2001 to January 2011 regarding sex, age, date of cancer diagnosis, tumor histology, primary site, time from beginning of immunosuppression, etiology of immunosuppression and survival,. Results: There were 46 patients (71.7% men). Median age was 47.1 years, 61% kidney transplant recipients and 39% HIV positive. The average time from the start of immunosuppression to the diagnosis of malignancy was 3.75 years in renal transplant recipients and 2.8 years in HIV positive patients. The most prevalent solid tumor in kidney transplant recipients was Kaposi's sarcoma (39.3%) followed by tumors of the gastrointestinal (GI) tract (21.4%) and genitourinary (GU) tract (14.2%). Kaposi's sarcoma was also the most prevalent cancer in HIV positive patients (44.4%) followed by head and neck (H&N) (22.2%) and GU tumors (11.1%). More than 50% of patients are alive and in follow-up. Conclusions: Kaposi's sarcoma, GI, GU and H&N tumors were the most prevalent solid neoplasms in immunosuppressed patients, in both organ transplanted and HIV patients.