bluuebunny/crossref_metadata_2025 huggingface dataset:
Empowered to stop smoking: The impact of a SDT smoking cessation intervention on economically disadvantaged whites and blacks
Authors: Figueroa-Moseley C. D. , Williams G. C. , Morrow G. R. , Jean-Pierre P. , Carroll J. , Ryan J.
Published: March 2020

1012

Background: Few studies have examined the potential influence of an empowering Self Determination Theory (SDT) intervention on reducing smoking behaviors and outcomes for Whites and Blacks. Objectives: To determine if empowerment to stop smoking is associated with smoking outcomes in Whites and Blacks, and to examine if empowerment to stop smoking improved under the SDT Intervention vs. Usual Care conditions. Methods: A longitudinal randomized trial study was conducted to examine the effect of a SDT and health behavior change intervention for tobacco cessation among adult smokers. Participants were randomized into the SDT Intervention or the Usual Care condition. The present study includes data from a sample of 821 Whites and 177 Blacks who completed anonymous surveys at 1, 6, and 18-months intervals on empowerment to stop smoking (Perceived Competence Scale, Treatment Self-Regulation Questionnaire), demographics, and smoking behaviors. Results: Stepwise logistic regressions showed that empowerment to stop smoking was associated with quitting smoking at 1, 6, and 18 month follow-up for both treatment conditions. At one month, participants in the SDT Intervention with the highest levels of empowerment were 6.3 times more likely to quit smoking as compared with those in the usual care condition who were only 3.15 times as likely to quit smoking. Similar findings were found at 6 months and at 18 months (6- month SDT Intervention Empowerment High: (OR = 8.66, 95% C.I. 4.6, 16.3); 6 month Usual Care Empowerment High: (OR = 3.10, 95% C.I. 1.4, 7.0); 18- month SDT Intervention Empowerment High: (OR = 4.10, 95% C.I. 2.2, 7.5); 18 month Usual Care Empowerment High: (OR = 3.11, 95% C.I. 1.3, 7.7). In the SDT Intervention at 6 months being Black increased successful quitting by 2.4 times. Conclusions: Findings indicate that at each time-point the SDT Intervention empowered more participants to stop smoking than usual care alone. Findings also suggest that Blacks may increase their ability to stop smoking in the SDT Intervention condition. These preliminary findings highlight the need to further investigate the possible roles of empowerment interventions in smoking cessation among Whites and Blacks, especially cancer patients.

No significant financial relationships to disclose.
Disclosure patterns and decision making preferences in BRCA 1/2 mutation carriers with young adult and minor children
Authors: Bradbury A. R. , Daugherty C. K. , Dignam J. , Ibe C. , Auh S. , Fay H. , Cummings S. A. , White M. A. , Olopade O. I.
Published: March 2020

1015

Background: Genetic testing of minors for adult-onset diseases has generally been discouraged. Yet, limited data suggests that many BRCA mutation carriers discuss their test results with their minor children. How parents make the decision to share this information and the effects on their health, their child and the family remains unknown. Methods: We sought to evaluate disclosure patterns and decision making practices among BRCA1/2 mutation carriers with children under the age of 25. 42 parents (with 86 children) completed a semi-structured telephone interview regarding communication of their genetic test results to their children. Chi-squared tests to assess associations between parent/child characteristics and disclosure were computed using robust variance estimates to account for clustering by family unit. Results: 55% of parents discussed hereditary risk of cancer and/or their genetic test results with at least one child. Factors associated with disclosure included older child age (p<0.001), female parent gender (p=0.049), parent history of prophylactic surgery (mastectomy: p = 0.021, oophorectomy: p<0.001) and education limited to high school (p=0.085). Child gender and parent’s history of cancer were not significantly associated with disclosure. Most participants reported themselves (45%) or their spouse (40%) as the most important person in the decision to disclose. Reports of physician (14%) and genetic counselor (21%) involvement were low. Conclusions: Parental decisions to disclose BRCA test results to children are complex and may reflect differences in perceptions of genetic disease. Further research is needed to understand parental motivations for disclosure and to define a role for health care professionals to improve counseling and recommendations regarding the risks and benefits of early communication of genetic risk to children.

No significant financial relationships to disclose.
Cancer risk management practices of non-carriers within BRCA1/2 mutation positive families in the Kathleen Cunningham Consortium for Research into Familial Breast Cancer (kConFab)
Authors: Dawson S. , McKinley J. , Jenkins M. , McLachlan S. , Lindeman G. , Friedlander M. , Hopper J. , Phillips K.
Published: March 2020

1020

Background: This study prospectively evaluated risk management practices of true BRCA1/2 negative women. Methods: A questionnaire was mailed to 471 non-carriers from mutation positive families 3 years after their enrolment in the kConFab breast cancer (BC) family cohort study. Women who had received their mutation result had pre-test counselling and result disclosure in one of 16 Family Cancer Clinics nationwide. Undertaking mammography more often than 2 yearly (Australian population guidelines), clinical breast examination (CBE) more often than yearly, breast self-examination (BSE) more often than monthly and any trans-vaginal ultrasound (TVU) or CA-125 was considered over screening. Linear logistic regression was used to identify factors (age, marital status, education, parity, ethnicity, place of residence, time since disclosure of result, family history) associated with over screening. Results: 347 women responded (74%); 260 were excluded from this analysis (self-reported not knowing their mutation status, 207; uninformative screening data due to proximity of result disclosure to questionnaire administration, 47; developed cancer, 3; pregnancy, 3), leaving 87 subjects. Mean follow up was 4.4 years. Proportions over-screening were; mammography 53%, CBE 10%, BSE 11%, TVU 10% and CA125 10%. No measured factor was associated with over-utilization of BC screening. Women with > one relative with OC were significantly more likely to over-utilize TVU (OR 8.1, CI 1.6–42 P=0.01) and CA125 (OR 19.6, CI 3.1–121 P=0.001) compared to women with ≤ one relative with OC. One woman underwent bilateral mastectomy and 1 bilateral oophorectomy; none used chemoprevention. Conclusions: A major benefit of learning one′s negative mutation status is that the intensity of risk management practices can be reduced to that appropriate for the general population. However, non-carriers with a strong family history of OC tend to inappropriately use OC screening. The reasons are unclear but need elucidation given the potential for harm. The reasons for over-utilization of mammography in 53% also warrant further study.

No significant financial relationships to disclose.
Automated data base screening of a population-based cohort of stage 1 colon cancer patients for eligibility in NSABP P-3, a polyp prevention study with celecoxib at Kaiser Permanente Northern California (KPNC)
Authors: Somkin C. P. , Gross R. , Liu H. , Fehrenbacher L.
Published: March 2020

1021

Background: Adjuvant/Prevention approaches should be designed to have broad applicability for maximum effectiveness. Celecoxib had generated interest as a polyp/colon cancer (CC) preventive agent. We used KPNC electronic data bases to identify consecutive Stage I CC patients and determine their eligibility for NSABP P-3, a polyp prevention study utilizing celecoxib in resected stage I CC. Methods: After IRB approval of both the P-3 study and use of KP data bases for recruitment, we prospectively screened all newly diagnosed CC patients within KPNC (1120 new patients a year) for stage I CC and P-3 eligibility. We identified 121 Stage I CC patients from 9/1/04 to 8/1/05 and using electronic data we screened these patients for 10-year life expectancy and other eligibility criteria. We confirmed each pathology diagnosis and stage by direct review. Results: Without chart review or patient history and exam, we found 65% of the patients were ineligible (IE) for any or multiple reasons. The average patient age was 68.9 years. 133 IE criteria were met by the 121 patients. 32% of patients were IE by age, though for only 11% was age the only criteria met. Other IE included 11% prior invasive CA, 19% coronary disease, 11% sulfa allergy, 8% coumadin usage, 7% prior CVA/TIA, 22% other GI or thrombotic criteria. It is likely that in-person history and examination would increase these IE numbers and reveal other barriers. Conclusions: Population-based automated eligibility analysis may be helpful in evaluating feasibility of chemoprevention and adjuvant trials and more importantly in determining their applicability to the whole population at risk.

No significant financial relationships to disclose.
Outcome-impact of a cervical cancer (CC) screening program (SP) in a developing country
Authors: Zarba J. J. , Holgado S. , Sanchez Segura M. , Gonzalez A. , Lorente C. , Monroy C. , Cano Busnelli V. , Elias A.
Published: March 2020

1032

Background: CC is the 2nd cause of cancer death in women in Argentine. Early detection following screening programs has demonstrated to reduce mortality in CC. The evaluation of the efficacy and efficiency of CC SP is associated with the proportion of positive cases in the smears and with the relation between pre-invasive lesion (CIN III) and invasive carcinoma (IC) in the biopsies done in positive cases. In 1997 a population based CC screening program was started in our province. The objective of this trial was to determinate the relationship between CIN III and IC in the program population and compare this results with this proportion in pre-program years an as an indicator of the quality of the program. Methods: We analyzed 2446 cervix biopsies performed in public Hospitals of Tucuman between 1985 and 2004 (archives of biopsies of the Serv. de Patología del Hosp. Centro de Salud Z. Santillán, Regional M. Belascuain and Hospital Angel C. Padilla), Since 1997 biopsies were done in patients within the SP We analyzed the proportions of pre-invasive lesions (CIN III) and invasive lesions in periods of 4 years. Results: The proportion of CIN III by periods of 4 years was: 85–88: 13%, 90–92: 20%; 93–96: 20%; 97–00 32% and 01–04 37%. The proportion of CIN III in pre-screening years was 21% and during the SP: 54%. Conclusion: These results shows an increase of CIN III over IC which could translate into a better survival. The quality control analysis of the public programs must be central in the public health policy.

[Table: see text]

No significant financial relationships to disclose.
Factor analysis in early detection of malignancies
Authors: Lazarev A. F. , Petrova V. D. , Sinkina T. V. , Selezneva I. A. , Terekhova S. A.
Published: March 2020

1033

Background: The existing methods of forecasting of malignancies and forming o of increased oncological risk groups are unserviceable for practical use because of their low reliability (no more than 84%). Methods: There was elaborated an original method for forming of increased oncological risk groups with reliability of 95%. It is based on factor analysis, including the data of phenotypes and genotypes, anamnesis, laboratory testing with further computer processing. The result lies in determination of a factor number. Its quantity forms figures of oncological risk rate. The dependence of risk rate on the quantity of a factor number is ascertained on the basis of data of more than 10000 observations ( table ). The patients with risk rate more than 80–90% are subjected to complex examination according to the elaborated algorithms. In case of absence of clinical symptoms of this or that organ lesion, each-organ search is being made in order to detect malignant neoplasms in accordance with their frequency on the territory of Altai region. Results: There were examined 4775 patients who happened to be in the zone of radioactive influence of Semipalatinsk nuclear testing ground (aged 43 years - 83 years old): male - 1639, female - 3136. 191 (4.0%) cases of cancer were detected: thyroid gland cancer - 56 cases, mammary gland cancer - 23, skin cancer - 49, uterine cervix cancer - 14, stomach cancer -11, lungs cancer -11, others -27. 5 cases of cancer in situ were revealed. Specific gravity of early forms of cancer was 96.5%. Conclusion: The research proved high effectiveness of the elaborated method for increased oncological risk group formation.

[Table: see text]

No significant financial relationships to disclose.
Phase II study of ixabepilone in patients (pts) with taxane-resistant metastatic breast cancer (MBC): Final report
Authors: Conte P. , Thomas E. , Martin M. , Klimovsky J. , Tabernero J.
Published: March 2020

10505

Background: Ixabepilone is the first epothilone analog in a new class of antineoplastic agents, which optimizes the properties of the naturally occurring epothilone B. The epothilones promote tumor cell death by uniquely binding to tubulin and stabilizing microtubules. Methods: This international, multicenter, open-label Phase II trial was designed to assess the activity of ixabepilone in pts with highly resistant MBC who had progressed following taxane treatment. Eligible pts were aged ≥18 years with MBC (progressed on or within 4 months of taxane therapy [or within 6 months if adjuvant taxane only]). Pts must have received a taxane as their last regimen. Pts were excluded if they had received ≥3 prior chemotherapy regimens for MBC or had ≥Grade 2 neuropathy. Ixabepilone was administered intravenously as a 3-hour infusion at a dose of 40 mg/m2 every 3 weeks. Results: Of 49 pts (median age 54 years, range 30–81), 86% of pts had received at least two prior chemotherapy regimens. 98% had received prior anthracycline treatment. 73% of pts had progressed within 1 month of their last taxane dose. 84% had visceral metastases. Pts received a median of three cycles (range 1–5) and median cumulative dose of 120 mg/m2 (range 40–498 mg/m2). The tumor response rate (number of responders [complete and partial response]/number of response-evaluable pts) was 12% (95% CI = 4.7–26.5%). All the responders (n = 6) had partial responses; five of the six had not responded to prior taxane therapy. The responders received a median of 10.5 cycles (range 5–15) and had a median duration of response of 10.4 months (95% CI = 6.3–22.0 months). In 20 pts (41%) stable disease was reported as the best overall outcome. The majority of these pts (16 of 20, 80%) received ≥4 cycles of ixabepilone therapy. The median time to progression was 2.2 months (95% CI = 1.4–3.2 months); the median survival was 7.9 months (95% CI = 6.1–14.5 months). Conclusions: Ixabepilone (40 mg/m2 as a 3-hour infusion every 3 weeks) demonstrates promising antitumor activity, along with an acceptable safety profile in pts with clearly defined taxane-resistant MBC.

[Table: see text]
Final efficacy results of a phase I/II trial of ixabepilone in combination with capecitabine in patients with metastatic breast cancer (MBC) previously treated with a taxane and an anthracycline
Authors: Bunnell C. A. , Klimovsky J. , Thomas E.
Published: March 2020

10511

Background: Ixabepilone is an epothilone B analog that has demonstrated efficacy in taxane-sensitive and taxane-resistant MBC. Differing mechanisms of action and minimally overlapping toxicities provide the potential for synergy between ixabepilone and other cytotoxics. Methods: This open-label Phase I/II study was conducted to determine the recommended Phase II (and III) doses of ixabepilone and capecitabine using a 3-hour infusion of ixabepilone given on Day 1 (Schedule A) or a 1-hour infusion of ixabepilone given for 3 consecutive days (Schedule B) in combination with capecitabine given orally on Days 1–14 every 21 days in patients (pts) with MBC previously treated with a taxane and an anthracycline in the adjuvant or metastatic setting. Pts were excluded if they had received >3 prior chemotherapy regimens in the metastatic setting. Tumor response was determined after every 2 cycles. Results from the 62 patients treated with ixabepilone 40 mg/m2 as a 3 hr-infusion and capecitabine 2000 mg/m2 are shown here. Results: 56/62 patients (90%) were aged <65 yrs. 80% of pts had visceral disease and 44% were ER/PR/HER-2 negative. 44% of pts had received ≥2 prior chemotherapies in the metastatic setting. Pts received a median of 4 cycles (range 1–20). The overall response rate was 30% (15/50; 95% CI = 17.9–44.6%) comprised of one (2%) complete response and 14 (28%) partial responses. All 15 of the responders had extensive tumor metastases at baseline. Four of the 15 responders were triple negative for ER/PR/HER-2. The median time to response was 6 weeks (range 5–14 weeks), with most responders achieving an objective response by the end of Cycle 2. The median duration of response was 6.9 months (95% CI = 4.3–9.7 months). Conclusions: The recommended Phase II (and III) doses were 40 mg/m2 ixabepilone (3-hour infusion on Day 1 every 21 days) and 2000 mg/m2 capecitabine (2 doses on Days 1–14 every 21 days). This ixabepilone/capecitabine combination demonstrated promising synergistic antitumor activity and a manageable safety profile in pts with MBC previously treated with a taxane and an anthracycline.

[Table: see text]
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.
Phase I pharmacokinetic (PK), and pharmacodynamic (PD) trial of the novel oral Notch inhibitor MK-0752 in patients (pts) with advanced breast cancer (BC) and other solid tumors
Authors: Krop I. E. , Kosh M. , Fearen I. , Savoie J. , Dallob A. , Matthews C. , Stone J. , Winer E. , Freedman S. J. , Lorusso P.
Published: March 2020

10574

Introduction: Activation of Notch signaling occurs in ∼40% of human BCs and high Notch expression is associated with poor outcome. Inhibition of Notch inhibits BC cell proliferation in vitro. Notch signaling requires gamma secretase (GS), which cleaves Notch, releasing the Notch intracellular domain (NICD) to activate transcription of target genes. MK-0752 is a potent GS inhibitor. Methods: In Part 1 of the study, pts with advanced solid tumors were enrolled using an accelerated dose escalation with 1 pt/dose level until the occurrence of ≥Grade 2 toxicity, then 3–6 pts/dose level. MK-0752 was administered by once-daily oral dosing in 28-day cycles. Once a maximum tolerated dose (MTD) was established, an additional 22 pts with advanced BC were to be enrolled in Part 2. Six-point PK plasma profiles were collected over 24 hours on Days 1 and 28 and assayed by LC/MS/MS. PD measurement of plasma Abeta40 peptide (another gamma secretase substrate) was performed pre/post dose on Days 1 and 28. Tumor biopsies on Days 1 and 28 were obtained from a subset of pts to assess changes in Notch activity by immunohistochemical analysis of NICD. Results: In Part 1, two pts were enrolled at 450mg daily, and five pts at 600mg daily. Dose-limiting toxicities (DLTs) were Grade 3 diarrhea, constipation, nausea, and abdominal cramping at 600 mg. In Part 2, an additional 14 pts with BC were enrolled at 450mg daily. In this cohort, Grade 2/3 fatigue requiring dose reduction occurred in 6 pts. Grade 3 diarrhea (1pt), nausea (1 pt) and elevated liver transaminases (2 pt) were also observed. Mean PK parameters (at 450mg, 600 mg) on Day 1 were AUC0–24hr = 1036, 1065μM·hr, Cmax = 72, 61μM, C24hr = 25, 32μM, and tmax = 3, 7 hr. PD measurements of GS inhibition showed a 12–78% (mean 46%) decrease in plasma Abeta40 at 4 hours on Day 1 compared to predose. Conclusion: Continuous dosing of MK-0752 at 450mg daily in pts with BC was associated with significant toxicity, predominantly fatigue, and cannot be considered a MTD. An intermittent dosing schedule is being explored. MK-0752 at all doses inhibited GS, as demonstrated by decreases in plasma Abeta40. Analysis of efficacy and intratumoral Notch inhibition will be reported at the meeting.

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Cost-effectiveness of letrozole and anastrozole as adjuvant therapy for hormone receptor positive early breast cancer in postmenopausal women
Authors: Delea T. E. , Karnon J. , Barghout V. , Thomas S. K. , Papo N. L.
Published: March 2020

10577

Background: The BIG 1–98 and ATAC studies demonstrated that, in postmenopausal women with hormone receptor positive (HR+) early breast cancer, 5 years of initial adjuvant therapy with the aromatase inhibitors (AIs) letrozole (LET) or anastrozole (ANA) is superior to tamoxifen (TAM). The cost-effectiveness TAM, LET, and ANA have not been previously evaluated using a consistent methodology. Methods: A Markov model was used to estimate the incremental cost per quality-adjusted life year (QALY) gained with initial adjuvant therapy with LET vs TAM, ANA vs TAM, and LET vs ANA in postmenopausal women with HR+ early stage breast cancer from the US healthcare system perspective. Probabilities of recurrence (including contralateral tumor) and adverse events (endometrial cancer, thromboembolism, fractures, hypercholesterolemia, MI, and stroke) for TAM were based primarily on published US population-based studies and trials of prophylactic TAM vs placebo. Corresponding probabilities for LET and ANA were calculated by multiplying probabilities for TAM by estimated relative risks of LET vs TAM and ANA vs TAM from the BIG 1–98 and ATAC trials respectively. Other probabilities, costs, and health-state utilities were obtained from published studies. Expected lifetime costs and QALYs were estimated for a cohort of HR+ postmenopausal women with early breast cancer, aged 61 years at therapy initiation and discounted at 3% annually. Probabilistic sensitivity analyses were conducted to assess precision of results. Results: Incremental cost per QALY gained for LET vs TAM is $33,536 (95% CI $20,409 to $70,566) and for ANA vs TAM is $38,967 (95% CI $23,826 to $81,904). Compared with ANA, LET is less costly ($9,647 vs $10,190) and gains more QALYs (0.29 vs 0.26), although differences in costs (95% CI -$1,669 to $671) and QALYs (95% CI -0.16 to 0.22) are not statistically significant. Conclusions: In postmenopausal women with HR+ early breast cancer, adjuvant therapy with either LET or ANA is cost-effective from a US healthcare system perspective. Although LET dominates ANA in our base-case analysis, definitive conclusions regarding the cost-effectiveness of LET vs ANA must await results of comparative clinical studies.

[Table: see text]
Long-term follow-up after intraoperative radiotherapy (IORT) for breast cancer
Authors: Kraus-Tiefenbacher U. S. , Herskind C. , Bauer L. , Melchert F. , Wenz F.
Published: March 2020

10594

Background: IORT for breast cancer with new treatment modalities is becoming increasingly important. In our department IORT is delivered by a mobile x-ray source (Intrabeam) producing isotropic 50 kV x-ray fields. Because this treatment modality includes single high doses to the normal breast tissue, careful evaluation of early and late toxicity is mandatory. Methods: Between 2/02 and 12/05 161 patients received IORT either as a tumour-bed boost (103) before 46 Gy external beam radiotherapy (EBRT) or as partial breast irradiation (58). Median age was 64.6 years (35–95), median tumour size was 15 mm (1–45). Spherical applicators (2.0 -5.0 cm diameter) were inserted into the tumourbed, giving a single dose of 20 Gy. Follow-up (f/u) included physical examination and ultrasound 1 week, 2 months, then every 6 months after therapy and mammography at yearly intervals. Radiobiological modelling of the expected spatial distribution of late reaction was done for typical cases using the linear-quadratic model with special consideration of relative biologic effectiveness, spatial dose distribution and dose rate. Results: Mean (f/u) time was 22 months. Minor postoperative side effects included erythema (5%), delayed wound healing (4%), mastitis (1%) and hematoseroma (4%). A fibrotic induration of the tumour bed was observed in 9, 18, 22, 23 and 26% of the patients at 2, 6 12, 24 and 36 month (f/u). Reoperation was required in 2 patients after 10 and 12 months, one mastectomy due to a fibrotic change of the whole breast and one local drainage of a fat necrosis. Conclusions: Although 2/3 of the patients were treated with a combination of IORT and EBRT, acute reactions in all patients were mild. Predominant late effect was an induration of the tumour bed which slowly began to resolve 1–3 years after therapy. The low level of clinically late reactions observed so far is in agreement with radiobiologic predictions from radiobiological modelling.

No significant financial relationships to disclose.