bluuebunny/crossref_metadata_2025_split huggingface dataset:
3-D irradiated lung and heart volume predictions from 2-D datasets: Value of CT-based treatment planning in postmastectomy tangential beam radiation therapy
Authors: Shankar V. , Haritha C. , Prajapati H. J. , Bhatt R. , Parmar J. , Shanubhogue A. 
Published: March 2020

11013 Background: Lung and heart complications in breast cancer treatment are directly related to the irradiated volumes, technique, total radiation dose and type of chemotherapy. 3D dose calcuations allow computation of the DVH’s & a realistic NTCP associated with breast cancer RT. 1) Study aims to evaluate the impact of the 2-D radiographic parameters on the volumetric dose of the lung and heart, for patients undergoing postmastectomy,postchemo radiation therapy. (2)To deduce the analytical equations for the quick estimation of the irradiated volume based on the distances obtained from the digitally reconstructed radiographs. Methods: Between August 2002–2006, 162 postmastectomy patients underwent 5wk course of tangential CW irradiation ± Axillary / SCL radiation to a total dose of 50gy/25#. After adequate immobilization on the CT compatable breast board, CT scans with 1cm slice intervalsof the chest were performed, covering lung apex to lung base. The ipsilateral total lung area and the lung area included within the treatment port were countered on each CT slice.It is multiplied by slice thickness, and then integrated in all CT slices to give volumes.Parameters used to deduce irradited lung volume (n=104) studied from the DRR included Central lung distance-CLD, Maximum perpendicular distance-MPD, Length of the lung-L & Parameters related to heart are measured only in left breast irradiation (n=58) included: Maximum heart distance-MHD, Maximum heart length MHL.Linear regression analysis is applied to test relationship between the percentage of ipsilateral lung volume involved and the CLD / MPD / L and similarly between MHD / MHL and the cardiac volume in irradiation. Results: Predicted irradiated volume for: Right Lung = 4.0118+6.6474(CLD) OR -5.965 + 6.827(MLD) Left Lung = 6.6395(CLD) OR 5.431(MLD) Heart = 7.325(MHD) OR 6.742(CLD) Conclusions: The conclusion of the present study, to the best of our knowledge, is the largest series reported so far in the literature. CLD and MLD deduced from the DRR, are the direct measures of the lung volumes irradiated in tangential breast irradiation ( r2=0.91 & 0.79).While MHD and CLD appear to be direct measure of the irraidiated heart volume (r2=0.98 & 0.91). No significant financial relationships to disclose.
Pathological characteristics and clinical outcome in triple-negative breast cancer (BC) patients (PTS): Results from the NORA study
Authors: Cazzaniga M. E. , Mustacchi G. , Pronzato P. , Di Costanzo F. , De Matteis A. , Ravaioli A. , Gamucci T. , Brugia M. , Bari M. , Rulli E. 
Published: March 2020

11014 Background: Different studies have recently focused the attention on the so-called triple-negative pts, defined as ER-/PR- /HER2-. Although triple-negative tumours have been reported to be more aggressive, there are limited long-term data evaluating outcome as a function of this classification. Methods: NORA is an observational study aimed at investigating treatment modalities and clinical outcome of 3515 patients (pts) with early breast cancer (EBC) treated in 77 Oncological Centres in Italy from to 2000 to 2003, whose overall results have been already published. We now compare pathological characteristics and clinical outcome of pts for whom ER and PR andHER2 tests are negative with remaining pts (OTH). Results: 123 (4.1%) of 2968 evaluable pts resulted triple-negative. Out of these 123, 76 pts (61.7% vs 63.2% of OTH) were treated with conservative surgery (CS). Pathological T stage was T1 in55.3% pts (OTH: 59.6%), 47.9% were pN+ (OTH: 45.3%), 63.2 had G3 tumours (OTH: 34.1%). Chemotherapy alone was administered in 89.4% pts, mainly anthracycline-based (54.1%). At a median follow up of 27 months, all triple-negative pts were alive, 11 (8.9%) with relapse. No difference has been observed between two groups both in DFS (HR=0.74; 95%CI: 0.39–1.40; p=0.35) and OS (HR not estimated, p=0.99). Conclusions: Our results suggest that triple-negative pts have pathological characteristics similar to what observed in the other pts, receive CS in the same percentage of the cases, but have a 3-fold increase of undifferentiated tumours. On the contrary to what observed by other Authors, our data show that triple- negative pts do not have worse prognosis. Longer follow up is required to confirm these data. No significant financial relationships to disclose.
Meta-analysis of side effects (SEs) of aromatase inhibitors (AI) and of tamoxifen (TAM) in large randomized clinical trials (RCT)
Authors: Vakaet L. A. 
Published: March 2020

11015 Background: The published data from large RCTs for the endocrine adjuvant treatment of postmenopausal breast cancer patients (ATAC and BIG 1–98) have shown us the difference in SEs between an AI vs TAM. Observed SEs in these trials are the result of an effect of both drugs: e.g. AIs induce bone loss and lead to an increase in fracture risk whereas TAM reduces fracture risk. We did a meta- analysis of comparable SEs in ATAC and BIG and combined this information with a second meta-analysis comparing an AI vs nil and a third meta-analysis comparing TAM vs nil. Methods: A relative risk (RR) meta-analysis was done on published data of SEs comparing AI vs TAM (ATAC Lancet 2002; BIG 1–98 NEJM 2005). SEs studied were: (1) fracture risk; (2) ischemic cerebrovascular events; (3) hypercholesterolemia; (4) hot flushes; (5) venous thromboembolic events and (6) any musculoskeletal events. Data for the comparison of AI vs nil were taken from MA.17 (NEJM 2003) and the combined arm of ATAC (Lancet 2002). Data for the comparison of TAM vs nil were taken from the P1 (JNCI 1998) and IBIS 1 (Lancet 2002). The assumption of a fixed effects model was used unless significant heterogeneity (Cochran Q test) was found. Results: In the comparison of fractures (ATAC and BIG combined) there was a 50% increase in RR for fractures in the AI arm. Our second meta-analysis showed that half of this increase was due to an effect of the AI and (according to the third meta- analysis) about half was due to a decrease of the RR for fractures thanks to TAM. Significant differences in cerebrovascular, hypercholesterolemia and hot flushes related events were due to a TAM effect. Concerning musculoskeletal events, significant heterogeneity was found when comparing the effect of an AI in the presence or absence of TAM. When patients get TAM together with an AI (ATAC combined arm) there is no increase in musculoskeletal events compared to the TAM alone arm. When an AI was compared to nil (MA.17) a significant increase in events was observed. We hypothesize that this heterogeneity is due to an estrogenic effect of TAM. Conclusion: This RR analysis allowed us to dissect the SEs profile of an AI and of TAM. The results for musculoskeletal events generate a new biological hypothesis. No significant financial relationships to disclose.
A study of pre-operative (neoadjuvant) letrozole in combination with bevacizumab in post-menopausal women with newly diagnosed operable breast cancer: A preliminary safety report
Authors: Forero-Torres A. , Percent I. , Galleshaw J. , Nabell L. , Carpenter J. , Falkson C. , Jones C. , Krontriras H. , De Los Santos J. , Saleh M. 
Published: March 2020

11020 Background: Our preclinical studies suggest that up-regulation of tumor cell VEGF is a mechanism to subvert estrogen dependence in hormone responsive breast cancer resulting in reduced efficacy or acquired resistance; we hypothesized that the combination of Bevacizumab (an anti-VEGF MoAb) and hormonal therapy would be more effective than hormonal therapy alone for breast cancer. Methods: Post-menopausal patients with ER and/or PR positive and Her-2-neu negative operable (T2–4a-c/N 0–2/M0) breast cancer were enrolled. Patients received letrozole (2.5 mg po daily) and Bevacizumab (15 mg/kg IV q 3 wks). Patients were reevaluated every 6 wks for a total of 24 wks; patients with CR/PR/SD in the first evaluation continued in the trial; after an additional 6 weeks of therapy patients with PD or SD were taken off-study and only patients with PR/CR completed 24 weeks of therapy. Definitive surgery was performed at the discretion of the surgeon no sooner than 4 wks after the last dose of bevacizumab. Patients continued letrozole while waiting for surgery. Up to December 2006, 27 patients have been enrolled with 13 patients too early to evaluate. Results: The 14 patients off-study had a median age of 63 years (range; 56 to 79) and an ECOG score of 0 for all patients. None of the patients received therapy for breast cancer before enrollment in the trial. 11 patients were stage II and 3 patients stage III. No treatment-related severe adverse events were seen. Treatment related toxicities were: grade 3 hypertension (n=1), grade 2 hypertension (n=7), grade 2 fatigue (n=2), grade 2 joint pain (n=3), grade 2 hot flashes (n=2), grade 1 proteinuria (n=1); 2 patients were taken off-study because of uncontrolled hypertension occurring on initial infusion of bevacizumab (not evaluable for efficacy). Of the 12 patients evaluable for response, 2 patients had pCR, 8 PR and 2 PD (at 9 weeks and 16 weeks). There have been no problems with wound healing or bleeding related to surgery or progressive disease while awaiting surgery. Conclusions: Combination letrozole and bevacizumab has substantial clinical efficacy and is well tolerated. The combination therapy will be evaluated in a randomized Breast Cancer Research Consortium Trial. [Table: see text]
Role of p53 mutations in clinical and pathological responses in an open-label study of capecitabine (C) and docetaxel (D) as neoadjuvant treatment for patients with recently diagnosed HER2-neu negative (HER2-) breast cancer (BC)
Authors: Truong S. , Patten N. , Tripathy D. , Gluck S. , Moisa C. , Wu L. 
Published: March 2020

11022 Background: The tumor suppressor gene p53 plays a key role in multiple cellular pathways controlling proliferation, survival, and genomic integrity. Disruption of its function promotes checkpoint defects, genomic instability and inappropriate survival leading to uncontrolled proliferation of damaged cells. The relationship of p53 mutation status to the outcome of patients suggests that p53 mutation status is a potential prognostic and predictive indicator of survival. Immunohistochemical analysis cannot accurately identify p53 mutation status and cannot differentiate between the several functional defects that arise from mutations at specific sites of this multifunctional gene. Methods: The primary objective is to define the rate of pCR in the affected breast after neoadjuvant C+D±T for HER2- or HER2+ BC pts, respectively. Eligibility: infiltrating HER2- or HER2+ stage II/III BC with no evidence of metastases and no prior systemic or local primary treatment. Four 3-week cycles consisted of C 825 mg/m2 bid on days 1–14 and D 75 mg/m2 on day 1. HER2+ pts also received T 4 mg/kg x1 on day -1 followed by 2 mg/kg weekly. Enrollment of 99 HER2- patients is planned. The AmpliChip p53 test (Roche Diagnostics, in development), a DNA microarray-based sequencing method, was used to analyze the p53 mutation status. The AmpliChip p53 test is designed to detect all substitution single base changes and single base deletion in all coding regions of the p53 gene. The genomic DNA was extracted from a biopsy sample from each patient and 50–100 ng genomic DNA was used. Results: A total of 47 p53 mutations were found in 44 of 88 (50%) patients, including 32 missense, 6 frameshift, 8 non-sense, and 1 splice site mutation, and were widely distributed in exon 2, 4, 5, 6, 7, 8, 9 and 10. The p53 mutation status including the type and location will be analyzed in relation to clinical and pathological response. Updated data will be presented. Conclusions: The AmpliChip p53 test is a rapid, accurate, and standardized way to detect p53 mutations. These findings suggest that p53 mutations occur in at least 50% of recently diagnosed BC. No significant financial relationships to disclose.
Anastrozole compared to tamoxifen as primary endocrine therapy for early operable primary breast cancer in the elderly
Authors: Ying M. , Agrawal A. , Winterbottom L. , Morgan D. A. , Ellis I. O. , Cheung K. 
Published: March 2020

11025 Background: The optimal management of operable primary breast cancer in elderly is controversial. A high proportion of elderly patients refuse or are unfit for surgery. However the majority have oestrogen receptor positive (ER+) cancer and respond extremely well to endocrine therapy. The use of tamoxifen as primary therapy is well established but its efficacy has not been compared with the newer aromatase inhibitors in this setting. We present the clinical data of the use of anastrozole when compared with tamoxifen in elderly patients as primary therapy for operable breast cancer. Methods: During a period of 2 years, elderly patients with ER+ operable breast cancer (<5cm), who either refused or were unfit for surgery, were given primary endocrine therapy. Tamoxifen was given by default but anastrozole was used when there were contraindications (eg thromboembolic and gynaecological risks). All had disease assessable to UICC criteria and were followed up in a dedicated clinic. Only patients who had treatment for =6 months (except for those who progressed prior) were included for analysis. Results: A total of 93 patients fulfilled the criteria for analysis thus far and the results are summarised as follows: 58 were given anastrozole and 35 with tamoxifen. At a median follow-up of 14.8 months (6 to 57), 8 patients have progressed. The results are summarised as follows: CR = complete response PR= partial response SD = stable disease Treatment was well tolerated in both groups and no patients withdrew due to side effects. Conclusions: The use of primary endocrine therapy in ER+ operable breast cancer in the elderly is highly effective. In this observational non randomised study there was no difference in efficacy detected between tamoxifen and anastrozole at this time, as seen in adjuvant trials. This may be due to the fact that majority of ER+ cancer in the elderly are highly ER rich as shown by high semi-quantitative scoring of immunhistological assays, making the superiority of the aromatase inhibitors less apparent. [Table: see text] No significant financial relationships to disclose.
Gemcitabine and concurrent radiation as a salvage treatment of chest wall recurrence in breast cancer
Authors: Shaharyar A. , Alauddin Z. , Shabbir K. , Hafeez M. , Rehman E. U. , Abbasi I. 
Published: March 2020

11027 Background: Chest wall recurrences are seen despite postoperative chemotherapy and radiotherapy. For patients with unresectable lesions who have previously received radiotherapy no standard treatment is available. We devised a protocol of low dose gemcitabine as radiosensitizer concurrent with low dose of radiation and conducted this study with the objectives to document the efficacy and toxicity of this protocol. Methods: From January 2003 to August 2005, 48 patients were included in this study. A histopthological or cytological evidence of chest wall recurrence was required. Females between 18–70 years, with previous modified radical mastectomy, post operative radiation and adjuvant chemotherapy were included. Patients with metastatic disease were excluded. Written informed consent was obtained. A dose of 150 mg / m2 of gemcitabine in 200 ml of normal saline was infused in 2 hour on day 1, 8, 15 and 22 of radiation. Radiation was delivered 2 hours after the completion of infusion. Conventional fractionation was used to deliver a total dose of 36 Gy given in 3.5 weeks. RECIST and RTOG criteria were used. Results: Twenty recurrences were related to the scar, 10 to the involved internal mammary lymph node region invading sternum and ribs and 18 were associated with the soft tissue masses outside the scar area. All patients were evaluable for response and toxicity. Complete response was seen in 6 (12.5 %) patients, (95 % CI, 13.87_37.16), partial response was seen in 30 (62.5 %) (95 % CI, 44.92 -71.40) with an over all response rate of 75 % (95 % CI, 70.57—91.40) Stable disease was seen in 9 (18.8 %) patients and disease progression in 3 (6.3 %) patients. Grade I skin reaction was seen in 15 (31.2 % ) patients grade II in 11 ( 22.9 % ) and grade III in 3 ( 6.3 % ) patients. No systemic toxicity was seen. Conclusions: Low dose gemcitabine and concurrent radiotherapy is a reasonable salvage treatment in chest wall recurrence in breast cancer patients who have previously received adjuvant chemotherapy and full dose of radiotherapy. This approach has acceptable toxicity. No significant financial relationships to disclose.
A multicenter pilot study of adjuvant docetaxel, epirubicin and cyclophosphamide (TEC) in patients (p) with stage II/III and node-positive breast cancer (BC)
Authors: Mayordomo J. I. , Lorenzo A. , Modolell A. , Alvarez I. , Bayo J. , Machengs-M Centelles-K Villadiego I. , Rubio M. J. , Heras L. , Yubero A. , Gonzálvez M. L. , Valero J. 
Published: March 2020

11029 Background: Based on wide experience with docetaxel, adriamicin and cyclophosphamide (TAC regimen) for adjuvant therapy of node-positive BC but taking into account the high incidence of febrile neutropenia and mucositis, we performed the present study with TEC aiming for a better toxicity profile at doses equipotent to TAC. Methods: 300 p with histological diagnosis of stage II-III BC, positive axillary lymph nodes, age 18 year old, ECOG PS 0–2 and adequate bone marrow, renal, hepatic and cardiac function were accrued after surgery. Prior chemotherapy, hormone therapy and radiotherapy for BC were not allowed. Treatment: T 75 mg/m2 iv d1, E 75 mg/m2 iv d1 and C 500 mg/m2 iv d1 every 21 days for 6 cycles. G-CSF 5 mcg/Kg /day s.c. was given on days 5 to 9. Results: Two hundred and one p having completed adjuvant therapy have been evaluated in this interim analysis. Median age: 53 years (range 25–77), ECOG PS 0/1 89%/11%, infiltrating ductal carcinoma 77%. Hormone receptor status was ER+ 79% and PR+ 60%. Surgery was mastectomy in 49% and conservative surgery in 51% of pts. Median number of positive axillary lymph nodes was 3. To date, 1,085 cycles were administered (median 6). Median relative dose intensity was 99% for T and 98% for E and C. There were 11 dose reductions for non- hematological toxicity and 4 for hematological toxicity. Toxicity: grade 3–4 neutropenia occurred in 15 p (7.5%), 8 of them were episodes of febrile neutropenia (4.0%). Other grade 3–4 toxicities per p were: leukopenia (7.0%), thrombocytopenia (0.5%), asthenia (6.5%), vomiting (4.5%), nausea (3.5%) and diarrhoea (3.0%). Four p (2.0%) discontinued therapy due to toxicity: 1 p with toxicodermic reaction, 1 p with hematological toxicity, 1 p with febrile neutropenia and 1 p with an allergic reaction to T. After study treatment, radiotherapy was administered to 63% of p and hormonotherapy to 66% of p. Conclusions: These preliminary results show that adjuvant TEC in p with stage II/III BC and positive axillary lymph nodes is feasible and well tolerated. No significant financial relationships to disclose.
Increasing tripartite cooperation of ER-alpha, c-Src, and IGF-1R plays an important role in tamoxifen resistance
Authors: Shu Y. , Yin Y. , Guo R. , Gu Y. , Liu L. , Wang R. 
Published: March 2020

11037 Background: Acquired resistance to tamoxifen is a serious therapeutic problem that limits its clinical benefit. The precise mechanisms for acquired tamoxifen resistance, however, are still not fully understood. Our prior studies suggest that enhancement interaction between growth factors and ERa was associated with development of tamoxifen resistance. Cross-talk between growth factor receptors and estrogen receptor alpha (ERa) makes this problem more complicated. We hypothesized that some other proteins may be involved in this association between two kinds receptors in the development of TAM resistance. Methods: To test our hypothesis, MCF-7 breast cancer cells were continuously treated with TAM (10–7 M) until the cells resist to tamoxifen treatment, which were named as tamoxifen resistant cells (TAM-R). Results: TAM-R cells were more sensitive to E2 and IGF-1 stimulation to express higher level phospho-MAPK than that of control cells. Inhibitory effect of AG1024 on TAM-R cells was about as 2 folds as many as that of control cells. MAPK inhibitor caused dramatic inhibition of growth of TAM-R cells. It was interestingly found that ERa translocated from nucleus to cytosol and an increased amount of ERa was co-immunoprecipitated with IGF-1R from TAM-R cells even though there was no change in the levels of these receptors compared to the control cells. c-Src was an important adapter protein between these two receptors, which increasingly combined with both IGF-1R and ERa in TAM-R cells. Pure antiestrogen ICI, AG1024/IGF-1R SiRNA, and Src family inhibitor PP2 could inhibit the interaction between IGF-1R and ERa. However, only PP2 could completely inhibit ERa translocate from nucleus to cytosol and cytoplasm membrane. Conclusions: Our results suggested that IGF-1R/MAPK signaling pathway was very important for TAM-R cells to develop resistance. c- Src was an critical elements to form a ternary complex with IGF-1R and ERa. This may be one mechanism responsible for tamoxifen resistance in breast cancer cells. No significant financial relationships to disclose.
Docetaxel (T) + capecitabine (X) with or without trastuzumab (H) neoadjuvant therapy for locally advanced breast cancer (BC): Phase II study
Authors: Lybaert W. , Wildiers H. , Neven P. , Amant F. , Christiaens M. , Van Limbergen E. , Weltens C. , Drijkoningen R. , Debrock G. , Paridaens R. 
Published: March 2020

11042 Background: In MBC, adding X to T improves RR, TTP and OS; adding X to TH improves TTP. XT±H is appealing in early BC because H serum concentrations fall during the peri-operative period, potentially reducing the risk of overlapping cardiac toxicity with adjuvant anthracyclines. Methods: Pts with newly diagnosed invasive stage III inoperable BC (cT4 and/or cN2–3) received six 21d cycles of oral X 900 mg/m2 bid d1–14 + iv T 36 mg/m2 d1&8 (+ H on d1 in pts with HER2+ [IHC 3+/FISH+] tumors: 8 mg/kg cycle 1, 6 mg/kg cycles 2–6). After surgery, pts received 4–6 cycles of FEC100 and radiotherapy (+ hormone therapy and H when indicated). Clinical response was assessed after cycles 3 and 6, safety after each cycle, and pathological complete response (pCR: no residual invasive tumor in breast and axilla) after surgery. Results: 71 of 89 planned pts have completed XT±H (Table); 64 have undergone surgery (53 mastectomies, 9 wide excisions, 2 axillary lymph node dissections only). 51 pts are evaluable for safety. The most common treatment-related adverse events (AEs; G1- 2/G3) were stomatitis (61%/8%), nausea (61%/6%), diarrhea (41%/22%), fatigue (57%/4%), neuropathy (59%/0), lacrimation (57%/0) and hand- foot syndrome (33%/16%). Other G3 AEs were anorexia (14%) and vomiting (10%); neutropenic fever occurred in 4 pts (8%). 24 pts had a dose reduction for G2–3 AEs (X 47%, T 27%). 7 pts stopped therapy prematurely for AEs. No unexpected AEs occurred with anthracycline-based adjuvant therapy. Conclusions: Although all pts experienced at least one AE, toxicity was predictable and manageable with dose reduction. Based on the encouraging efficacy of XT+H in HER2+ pts, we are expanding this arm. [Table: see text] No significant financial relationships to disclose.