bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blood oxygen level dependent (BOLD) contrast MRI and breast cancer chemotherapy response
Authors: Tripathy D. , Jiang L. , Rao N. , McColl R. , Xie X. , Weatherall P. , Story M. , Ding L. , Mason R. 
Published: March 2020

10514 Background: Tumor microcirculation and oxygenation play critical roles in tumor growth and response to cytotoxic treatment. Assessing these parameters in vivo may provide a useful tool for evaluating therapy in real time. Deoxyhemoglobin (dHbO2) can serve as an endogenous contrast agent causing signal loss in echo planar MR images. Tumor characteristics or interventions affecting tumor oxygenation, which convert dHbO2 to HbO2 produce a BOLD signal gain, may complement conventional MRI. Material and Methods: Ten patients with locally advanced breast cancer received doxorubicin and cyclophosphamide (AC) for four cycles every 2 or 3 weeks followed by paclitaxel for 4 cycles. Prior to chemotherapy and after 1 and 4 cycles of AC, MRI was performed on a 1.5 T scanner. For the BOLD study, patients breathed room air (RA) for 45 sec, then oxygen for 6 min and finally RA again. The BOLD imaging an Echo Planar technique with TR/TE (500/41.4 ms) 256 matrix and 20cm field of view. This was followed by dynamic contrast enhanced (DCE) MRI study. Pre and 1 to 4 day post-treatment tumor biopsies for hypoxia response proteins by immunohistochemistry and global RNA by gene array expression analysis (Illumina platform) were obtained. Results: MRI showed mild BOLD contrast enhancing regions in all evaluable patients with a typical signal enhancement of ∼2%. All 3 patients with an initial high BOLD-effect (>7%) achieved a pathological response after chemotherapy compared to 4 who did not (p < 0.03). The MRI-DCE tumor response signal decreased with chemotherapy, but no correlation with pathological response was seen. No clear difference in hypoxia-induced proteins (eg. HIF1-alpha, VEGF, CAIX) was seen according to pathological response or BOLD. Distinct gene expression patterns at baseline and after therapy emerged depending on BOLD response involving development, apoptosis and cell cycle pathways. Discussion: BOLD MRI can provide a non-invasive, easily repeatable in vivo approach to assess breast tumor physiology and its sensitivity to hypoxia (vascular oxygenation) may add value by measuring hypoxia and predicting response to therapy. BOLD MRI appears promising to select ideal candidates for hypoxia targeting with anti-angiogenic agents combined with chemotherapy and such studies are under way. No significant financial relationships to disclose.
A phase II study of neoadjuvant docetaxel/carboplatin with or without trastuzumab in locally advanced breast cancer: Response and cardiotoxicity
Authors: Chang H. R. , Slamon D. , Prati R. , Glaspy J. , Pegram M. D. , Kass F. C. , Bosserman L. D. , Taguchi J. , Dichmann R. , Chung D. 
Published: March 2020

10515 Background: A phase II clinical trial was conducted to study the safety and efficacy of neoadjuvant docetaxel/carboplatin (T/C) with or without trastuzumab (H) in women with stage III breast cancer. Methods: Forty-eight of 75 planned primary breast cancer patients (T3 or T4, any N, M0), age between 18 and 80 have been enrolled. Four cycles of T (75 mg/m2) + C (AUC 6) were given every 3 weeks preoperatively. Patients with HER-2 amplified tumors (FISH +) were randomized to receive either weekly concurrent H or T/C alone preoperatively and T/C plus H postoperatively. Tumors were assessed clinically at baseline and after neoadjuvant therapy. Cardiac assessment consisted of medical history, EKG and LVEF (by echocardiogram or MUGA) at baseline and at the end of neoadjuvant chemotherapy. Results: Available data from 45 of 48 enrolled patients showed 49% (22 cases) with complete clinical response, with 54.5% being HER-2 (+) (12 cases). Stable disease was seen in one patient who was HER-2 (−) (2.2%). Of 37 with complete pathology verification, 11 (29.7%) showed pathologic complete response (pCR) of the primary tumor with 5 cases being HER-2 (+). Of the 22 HER-2 (+) cases that completed neoadjuvant treatment, 11 received T/C/H and 11 received T/C. pCR was noted in 36.4% of the T/C/H group and 9% of the T/C group. LVEF data is available from 43 patients during the neoadjuvant phase, showing 18.6% (8 cases) with decrease of ≥ 10% (5 patients in the T/C arm and 3 patients in the T/C/H arm), although none had cardiac symptoms or LVEF below the normal limit. Conclusions: T/C ± H is clinically active in patients with locally advanced breast cancer including a 30% pCR rate. The cardiotoxicity rates were comparable between patients who received T/C and T/C/H. No significant financial relationships to disclose.
Minimal arm lymphedema after breast conservation therapy
Authors: Bar Ad V. , Cheville A. , Amin N. , Booty J. , Solin L. J. , Harris E. E. 
Published: March 2020

10527 Background: Arm lymphedema (ALE) is a serious consequence of the treatment for breast carcinoma. The objective of the current retrospective study was to analyze the time-course of minimal ALE after breast conservation treatment for early stage breast cancer. Methods: The study cohort was drawn from consecutive stage I or II patients who underwent breast conservation therapy including axillary staging followed by radiation. During follow up assessments after treatment, measurements of arm circumference were frequently performed at regular intervals, for clinically evident swelling of the arm or for complaints of swelling of the arm. ALE was documented in 274 of 1861 (15%) patients. 109 patients, 6% of overall group, and 40% of the patients with lymphedema, presented with minimal ALE, defined as a difference of 2 cm or less between the affected and unaffected arms. Results: The median age of patients was 54 years. The median interval to develop ALE was 1 year. The median follow up was 11 years. Among all 109 patients with minimal grade ALE at the time of ALE diagnosis, 21%, 13% and 14% of the patients progressed to more severe grades of lymphedema after 1,3 and 5 years of follow-up, respectively (See table). 40% of the patients with minimal grade ALE received therapy for lymphedema. Despite treatment for minimal grade ALE, 37% of treated patients progressed to more severe grades of lymphedema at 1 year follow up, and 24% progressed at 3 and 5 years follow up. Conclusions: Minimal ALE after breast conservation therapy, including axillary staging, developed in 6% of stage I or II breast cancer patients. Minimal ALE has the potential to progress to more severe grade of ALE. Despite treatment for lymphedema for minimal grade ALE, some patients still progressed to more severe grades of lymphedema. [Table: see text] No significant financial relationships to disclose.
Clinical response at 4 months to neoadjuvant letrozole predicts distant disease free survival in postmenopausal women with stage II-III ER/PgR-positive breast cancer
Authors: Guillem V. , Llombart-Cussac A. , Lopez Guerrero J. , Guerrero A. , Fuster C. , Ruiz A. , Climent M. A. , Tena I. , Vazquez C. , Llombart-Bosch A. 
Published: March 2020

10531 Background: Letrozole (L) is more active than tamoxifen in early stage ER[+] breast cancer both as adjuvant (BIG-98 trial) or neoadjuvant (LET-024) therapy. However, complete pathological remissions to neoadjuvant endocrine therapy are anecdotal (<5%), there are no new prognostic indicators with clinical implications. Methods: We have review our series of postmenopausal patients with stage II-III breast cancer ER/PgR[+] breast cancer treated in our institution with L as neoadjuvant therapy. All patients had completed 4 months of therapy (in the absence of PD), and had measurable clinical (or radiological) disease. An independent statistical analysis was conducted for disease free (DFS) and distant disease free survival (DDFS). Results: From IV/99 to XII/04, 107 patients fulfill the criteria. Median age 76 years (range 64 to 92); median tumour size 35 mm (range 25 to 100); cT2 75 (70%), cT3/4 32 (30%); cN[-] 83 (78%). The ORR (PR + CR) at 4 months was 63% (7 CR and 60 PR), 4 patients had PD as best response (4%) and 36 a SD (34%). Surgery was done in 63 patients (59%), including all non-responders. Only 2 patients received adjuvant CT. With a median follow-up of 32 month (range 8 to 66), 12 patients had relapsed (9 distant). The 3 years DFS and DDFS were 84% and 90% respectively. In univaried analysis: cN (p < 0.02), cT3/4 (p < 0.02), and clinical response at 4 months (CR) (p = 0.003) were related to DFS; and HER2 (p < 0.05), cN (p < 0.003), and CR (p = 0.007) with DDFS. Other factors like cT, HR-levels, or surgery were not significant. Multivariate analysis showed that only OR and cN remained independently predictive both for DFS and DDFS. Conclusions: Clinical response to neoadjuvant letrozole therapy is an independent predictor of distant disease free survival and could be of value to recommend or deny more aggressive therapies in addition to endocrine therapy. [Table: see text] No significant financial relationships to disclose.
Understanding decision supports (DS) for women with breast cancer eligible for clinical trials (CT)
Authors: Wright J. , Dimitry S. , Sussman J. , Whelan T. J. 
Published: March 2020

10534 Background: CTs are vital to the development of treatments for patients with cancer, but a low proportion of patients participate in trials, resulting in decreased access to new options. Methods: The study purpose was to explore DS for CT participation decision-making with women diagnosed with breast cancer who were offered a CT. 31 women took part in 6 focus groups - 3 groups of women who consented to a CT, 3 groups who declined a CT. Open-ended questions were asked about specific DS and ideas for new ones. Information rich cases were selected for the sample. Data analyses were conducted by 2 independent coders using a line-by-line, open coding process. Reliability was checked by a 3rd coder. Data was organized with template and editing approaches. Results were compared by group type (declined/consented to CT). Results: Common themes emerged from both group types: too much information is given at the first oncology consult; patients prefer to get CT information from the cancer centre, after their surgery, but prior to their oncology consult; no strong preference about who acts as a DS—family doctor, surgeon, other—as long as good relationship exists; oncologist (to lesser degree surgeon) is seen as most informed about their case; preference for oncologist vs trials nurse to describe CT concept, answer questions, direct them to other information sources; patients doubt family doctors or surgeons have detailed knowledge of CTs, know specific trial data; patients want to feel prepared, know what may happen before they come to oncologist - consult process, CT may be option - to avoid surprise; helpful to know that there is time to make CT decision; other patients are a good source of DS and information. Conclusions: Patients had strong preference to receive information about CTs prior to their consultation with an oncologist; this timing was seen as helpful for decision-making about a CT by both group types. No significant financial relationships to disclose.
Interstitial high dose rate (HDR) brachytherapy for early stage breast cancer
Authors: Biggs S. , Anderson P. J. , Mark R. , Neumann T. , Nair M. 
Published: March 2020

10551 Background: External Beam Radiation Therapy (EBRT) has been the standard of care for breast conservation radiation therapy. Recent data indicates that Interstitial Implant and High Dose Rate (HDR) radiation afterloading compares favorably to EBRT in selected patients. Methods: Patients with Tis, T1, and T2 tumors measuring ≤ 3 cm, negative surgical margins, and negative axillary lymph nodes were judged to be candidates for Interstitial Implant. Results: Between 2000 and 2006, 112 patients underwent Interstitial HDR Implant under Stereotactic Mammographic guidance with conscious sedation and local anesthesia. Conscious sedation consisted of Morphine and Versed. Local anesthesia was given with a mixture of 1% Lidocaine, 0.25% Marcaine, 1:100,000 Epinephrine, and 4% Sodium Bicarbonate neutralizing solution. The implants were placed using a Template with from 3 to 6 planes, and 8 to 43 needles. Catheters were subsequently threaded thru the needles, and the needles removed. Catheter spacing was 1.0 to 1.5 cm. Radiation Treatment planning was performed using CT Scanning. Treatment volumes ranged from 25 cm3 to 359 cm3. The breast implant volume received 3400 cGy in 10 fractions via HDR prescribed to the Planning Target Volume, given BID over 5 days. The procedure was well tolerated. No patient required hospital admission. With a median follow-up 36 months (range 6–60 months), local recurrence occurred in 2.7% (3/112). Cosmetic results were good to excellent in 85.7% (96/112) of the patients. Wound healing complications developed in 7.1% (8/112). Three of these patients had received anthracycline based Chemotherapy. The other five had large (> 200 cm3) implant volumes and catheter spacing of 1.5 cm. Two patients healed after 6 months of conservative treatment. Surgery was required in six patients who developed fat necrosis. Conclusions: With median 36 month follow-up, Breast Conservation radiation therapy utilizing Interstitial HDR Implant has yielded local recurrence rates and cosmetic results which compare favorably to EBRT in selected patients. Treatment with anthracycline based Chemotherapy and large (> 200 cm3) implant volumes appear to be relative contraindications to Interstitial HDR Implant. Finally, catheter spacing of 1 cm yielded optimal dosimetry and minimized complications. No significant financial relationships to disclose.
Tumor markers in metastatic breast cancer: High tumor specificity within the reference range
Authors: Stieber P. , Nagel D. , Heinemann V. 
Published: March 2020

10554 In breast cancer as well as in other solid tumors all “tumor markers” actually available are not tumor specific but can be measured in different extent also in all healthy individuals. By consequence any fixed cut off value used must lead to false positive and negative test results for the individual patient. In a retrospective analysis we investigated the diagnostic capacity of CEA and CA 15–3 for the early detection of metastatic breast cancer comparing the use of fixed cut off values with kinetics. After complete removal of the tumor (R0 resection) breast cancer patients reach 4 weeks after the end of adjuvant radio/chemotherapy their individual “normal” values: these median values for CEA (Abbott, AxSYM) and CA 15–3 (Roche, Elecsys) are comparable to the medians of healthy individuals (CEA: 1 ng/ml; CA 15–3: 13 U/ml). A reproducible increase of 100% of at least one of these markers was postulated as indication for metastatic disease. A total of 899 breast cancer patients with a non metastatic primary tumor and available individual baseline values after primary treatment was included. Of these 717 remained disease-free and served as control group, whereas 182 patients developed metastatic disease during follow-up. On this basis we reached a specificity of more than 98% for both biomarkers and a sensitivity of 16% for CEA alone, 24% for CA 15–3 alone and another 25% for both markers resulting in 66% true positives or 34% false negatives. Using fixed cut off values (CEA: 4 ng/ml and CA 15–3: 30 U/ml) we ended up with 19% false positives (specificity 81%) and a sensitivity of 9% for CEA, 30% for CA 15–3 and another 27% for both resulting also in 34% false negatives. Using higher cut off values where the probability of metastatic breast cancer is increased (CEA: 6 ng/ml and CA 15–3: 60 U/ml) we reached a specificity of 96% and a sensitivity of 10% for CEA and 19% for CA 15–3, another 14% for both, resulting in 57% false negatives. We conclude that the interpretation of these markers in follow-up care using individual baseline values and kinetics leads to a significant superior profile of specificity and sensitivity. No significant financial relationships to disclose.
Gamma Knife stereotactic radiosurgery in the treatment of brain metastases from breast cancer
Authors: Gutt R. , Yovino S. , Chin L. , Regine W. , Amin P. , Tkaczuk K. , Kwok Y. 
Published: March 2020

10555 Background: Outcomes of gamma knife stereotactic radiosurgery (GK-SRS) for patients with brain metastases specifically from breast cancer have not been well-defined. This study was undertaken to report the long-term experience with GK-SRS in this subset of patients. Methods: From 1995 to 2005, 75 patients with 162 brain lesions were treated with GK-SRS at the University of Maryland Medical Center. Complete follow-up data were available in 65 patients. Additional whole brain radiation therapy (WBRT) was administered to 53 (81.5%) patients. The median WBRT dose was 36.75 Gy (30.0–45.0 Gy). The median number of lesions treated with GK-SRS was 2 (1–8 lesions). The median follow-up, age, and KPS were 7.2 months (0.4–75.7 months), 53.5 years (23–81 years), and 90 (40–100), respectively. The factors included in the univariate and multivariate analyses for overall survival (OS) and progression free survival (PFS) were age, Karnofsky Performance Status (KPS), tumor histology, estrogen receptor status, Her-2-neu status, number of intracranial lesions, and presence of systemic disease. Results: Median PFS and OS from GK-SRS were 5.3 months (0.4–33.2 months) and 8.1 months (0.4–75.7 months), respectively. The 6, 12, and 24 month actuarial PFS were 47.8%, 24.9%, and 9.6% respectively. The 6, 12, and 24 month actuarial OS were 60.7%, 39.1%, and 18.1% respectively. The tumor local control after WBRT and GK-SRS was 87.7%. Radiation necrosis was a complication in 10.8% of patients. Forty-seven (72.3%) patients had neurological symptoms prior to gamma knife treatment. Seven (14.9%) and 9 (19.1%) of these patients experienced symptom resolution and significant symptomatic improvement, respectively. Multivariate and univariate analysis did not reveal any of the prognostic factors in question to be significantly associated with OS nor PFS. Conclusions: This relatively large cohort of patients experienced poor survival outcomes despite aggressive therapy with WBRT and GK-SRS. However, GK-SRS can provide significant symptomatic relief, with acceptable complication rates. More research is required to improve the survival of breast cancer patients with intracranial metastases. No significant financial relationships to disclose.
Clinical outcomes following immediate reconstruction and post-mastectomy radiation therapy
Authors: Jhaveri J. D. , Savetsky I. , Bosworth J. L. , Rush S. C. 
Published: March 2020

10560 Background: Post-mastectomy radiation therapy (PMRT) is an important component of the treatment for locally advanced breast cancer. Some patients opt for immediate breast reconstruction (IR) to cope with the aesthetic consequences of mastectomy. A small number of series have reported mixed results with IR using a tissue expander/implant (TE/I) followed by PMRT. We sought to determine the outcome of patients receiving PMRT after IR with either TE/I or autologous tissue reconstruction (ATR), with respect to both complications and cosmesis. Methods: We retrospectively reviewed the charts of 47 women who underwent PMRT in our practice after IR. All follow-up information was obtained by reexamination or by telephone interview. Contracture/fibrosis results were scored on a scale as follows: 0- no complaints, 1- mild discomfort, not affecting activities of daily life (ADLs), 2- moderate discomfort, affecting ADLs, or biopsy-proven fat necrosis, 3- complications requiring surgical revision, 4- reconstruction failure, requiring removal. For cosmesis, results were recorded as: 1- acceptable, 2- unacceptable. Results: A total of 47 patients were identified as having undergone PMRT after IR. 35 underwent TE/I and 12 underwent ATR, most commonly transverse rectus abdominus muscle flap reconstruction. Median follow-up was 36 months (range: 26 - 96 months). All patients were treated with 50.4 Gy in 25 fractions to the chest wall, and seven patients received an additional electron boost to high risk areas. All patients received 45 Gy in 25 fractions to a supraclavicular field. Of the patients who underwent TE/I and PRMT, twenty-one of 35 (60%) described unacceptable cosmesis, as opposed to two of 12 ATR patients (17%) (p = .02). Similarly, 13 patients in the TE/I (37%) group required either surgical revision (n = 3) or complete removal of their implant (n = 10), as compared to none of the patients in the ATR group (p = .02). Conclusion: Immediate TE/I reconstruction with PMRT was associated with high rates of complications and poor cosmetic results in our experience. ATR resulted in significantly higher rates of functional and cosmetic success. Thus, if IR is planned in the setting of PMRT, ATR should be recommended. No significant financial relationships to disclose.
Effect of microscopic residual tumor (MRT) at surgical margin of resection (SMR) in invasive breast cancer (IBC) on survival of non-Hispanic white women in central Pennsylvania (PA)
Authors: Ingle A. M. , Kumar P. , Baney B. , Day K. , Dagen T. , Galley A. S. , Dixon R. H. 
Published: March 2020

10569 Background: Few studies that have investigated the long-term effect of MRT in IBC, have demonstrated conflicting results. Mount Nittany Medical Center (MNMC) is located in an agricultural, ethnically-homogenous (Non-Hispanic White) county in PA. To the best of our knowledge, there have been no similar studies conducted on such populations. Our study has investigated the effect of MRT at SMR on overall survival (OS) and event-free survival (EFS) of patients with IBC. Methods: All women diagnosed with IBC from 04/1992 to 06/2005 at MNMC were deemed eligible. Log-rank statistics and Cox proportional hazard models (CPHM) were used for obtaining survival rates. Results: Of the 939 eligible women analysis were performed on 651 women (age range 27–94 years; median 62 years) with complete data on diagnosis, surgical margins and treatment modalities. With a median follow-up time of 4 years (range 0.01–11.3 years), 390 (59.9%), 214 (32.8%), 47 (7.2%) women had stage I, II and III tumor respectively; 540 (83%) patients had no residual tumor at SMR. 484 (74.4%) patients received radiation therapy (RT) ± chemotherapy (CT) and/or hormonal therapy (HT), 383 (58.8%) received HT ± CT and/or RT and 229 (35.2%) received CT ± RT and/or HT. The CPHM demonstrated no statistical significance of MRT on OS (hazard ratio 1.54, p = 0.07), and EFS (hazard ratio = 1.54, p = 0.07) after adjusting for treatment, stage and age. Univariate 10-year OS rate in patients with no MRT was 72.7% (95% confidence interval (CI) 63.1% to 80.1%), versus 61.2% (95% CI 45.3% to 73.8%) in patients with MRT (p-value = 0.07). Ten-year EFS was observed to be 68.9% (95% CI 59.1% to 76.8%) in patients with no MRT, versus 60.8% (95% CI 45.1% to 73.2%) in patients with MRT (p-value = 0.08). Conclusion: In our study, patients with IBC with MRT at SMR have a 1.5 times the risk of death or recurrence as compared to patients with no MRT. However, this difference is statistically not significant over time. No significant financial relationships to disclose.