bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P2-11-08: Feasibility of Enrollment Into a Survivorship Care Plan Study at Initial Diagnosis
Authors: Bulloch KJ , Irwin M , Chagpar A , Sanft T
Published: August 2014

Introduction: The Institute of Medicine currently recommends all cancer survivors be provided survivorship care plans (SCPs) to aid them in their transition from cancer patient to cancer survivor. To our knowledge, there are very few comprehensive cancer treatment centers that report having a system that insures all patients will receive SCPs. One of the chief obstacles in broadly providing care plans is logistical; not all breast cancer patients undergo the same treatment progression and thus it is difficult to identify a suitable time after which the provider should distribute SCPs. Though adjuvant treatment pathways differ between patients, nearly all breast cancer patients receive surgery and thus surgery clinics could provide an opportunity to identify the majority of patients who will eventually be cancer survivors. The purpose of this study is to assess the feasibility of providing SCPs to breast cancer survivors by enrolling them at the postoperative visit and tracking them prospectively throughout their treatment.

Methods: 75 English-speaking women over the age of 18 with stage I-III breast cancer were enrolled at their postoperative appointment. The participants' treatment progress was tracked through the electronic medical record; the treatment information was abstracted from the records and used to create treatment summaries. Once treatment was completed, participants received the SCP during one of their scheduled follow-up appointments.

Results: Accrual occurred during 42 clinic days between April 2011 and February 2012. During that time, there were 129 postoperative appointments for patients with a diagnosis of breast cancer. 54 did not meet the eligibility requirements; 46 were DCIS, three had metastatic cancer, and five did not speak English. Of the patients who met the eligibility requirements 100% agreed to participate. Characteristics are shown in Table 1.

Only 39.4% of participants received both chemotherapy and radiation and 9.6% of our participants received their adjuvant therapy outside of Smilow Cancer Center.

Conclusion: Women recently diagnosed with breast cancer are interested in receiving survivorship care plans after treatment, as demonstrated by 100% accrual rate of eligible patients approached in the postoperative visit. The postoperative visit in a surgical clinic may provide the starting point for tracking a patient through treatment.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-11-08.
Abstract P2-11-10: Prospective memory impairment in early breast cancer survivors: Finally homing in on the real deficit?
Authors: Verma S , Collins B , Song X , Bedard M , Paquet L
Published: August 2014

Background There is still much debate about the impact of early breast cancer (EBC) treatment on memory functioning. One limitation of existing studies is that they are based on neuropsychological testing procedures which may not be sensitive enough to detect memory problems as encountered in daily life. In fact, no study has objectively assessed everyday memory performance in EBC. One crucial aspect of using memory in daily activities is to remember to do something at an appropriate time in the future without being asked to do so-defined as “prospective memory” (PM). Despite its importance for daily functioning, little is known about PM in EBC patients. Thus, we investigated whether EBC survivors who were within 1 year of having completed adjuvant chemotherapy have PM impairment in comparison to age-matched healthy controls. In addition, we evaluated the contributions of fatigue and depression to PM functioning.

Methods We undertook a cross sectional quantitative case-control study (n = 80) comparing EBC patients from the Ottawa Hospital Regional Cancer Centre with age and education-matched healthy controls from the community. A standardized test of PM (Memory for Intention Screening Test) was administered to both groups. Impairment was defined as a score that fell 2 standard deviations below the mean performance of the control group. Standardized measures of depression (CESD) and fatigue (Fact-F) were also completed.

Results Age was well balanced between the groups (case and control mean age 54y, p = .84). EBC patients performed more poorly than controls on the PM test (p < .001) and had a significantly higher rate of impairment (23% vs. 5%, McNemar χ2, p <.01, odds ratio=5.5, 95% CI=1.7745 to 17.1473). A series of hierarchical regressions showed that patients PM performance was affected by fatigue (p <.05), but not depression (p = .51).

Conclusions The results demonstrate reduced memory performance in EBC survivors, with a specific impact on PM. Women who complain of ‘chemo fog’ should be evaluated carefully for PM deficits and their concerns should be acknowledged. An important finding from this study is the demonstration that fatigue is associated with memory deficits when memory as used in everyday life is evaluated. This finding which is suggestive of a common mechanism involved in fatigue symptoms and everyday memory disturbances raises the possibility that interventions targeted at improving fatigue may also improve memory functioning and quality of life in EBC survivors. Further longitudinal studies should be conducted to critically evaluate the role of chemotherapy by assessing PM before the initiation of chemotherapy and in EBC patients receiving only adjuvant hormonal therapy.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-11-10.
Abstract P2-12-04: Music Therapy Reduces Radiotherapy-Induced Fatigue in Patients with Breast or Gynecological Cancer: A Randomized Trial
Authors: Freitas NMA , Silva TRMA , Freitas-Junior R , Paula Junior W , Silva DJ , Machado GDP , Ribeiro MKA , Carneiro JP
Published: August 2014

BACKGROUND: Fatigue is a frequent side effect of radiotherapy, and may interfere with self-esteem, social activities, and quality of life. The authors investigated the influence of music therapy (MT) on the reduction of fatigue in women with breast or gynecological malignant neoplasia during radiotherapy.

METHODS: Randomized controlled trial (control group-CG and music therapy group-MTG) to assess fatigue, quality of life using the Functional Assessment of Cancer Therapy (FACT-F and FACT-G) version 4 and symptoms of depression using Beck Depression Inventory (BDI) in women undergoing radiotherapy in three distinct moments (during the first and the last week of radiotherapy, and on the week of the intermediary phase). Individual 30–40 minute sessions of music therapy were offered to participants of the MTG.

RESULTS: In this study, 164 women were randomized and 116 (63 CG and 53 MTG) were included in the analyses, with mean age of 52.9 years (CG) and 51.85 years (MTG). Participants in the MTG had an average of 10 MT sessions, during the study. FACT-F results were significant regarding Trial Outcome Index (TOI), synthesis of the Physical and functional well-being areas of FACT-F (p = 0.011), FACT-G (p = 0.005), FACT-F (p = 0.001) for MTG compared with CG. The depressive symptons were reduced to the minimum levels in the MTG (p = 0,005) with risk reduction of 74% (RR = 0,26; CI 0,10–0,70).

CONCLUSIONS: Individual MT sessions are effective to reduce fatigue related to cancer and symptoms of depression, as well as to improve quality of life for women with breast or gynecological cancer undergoing radiotherapy.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-12-04.
Abstract P2-12-13: Results of randomised controlled phase II study (KBCSG02 trial) of the efficiency of palonosetron, aprepitant, and dexamethasone for day1 with or without dexamethasone on days2 and 3.
Authors: Kosaka Y , Sengoku N , Kikuchi M , Nishimiya H , Enomoto T , Kuranami M , Watanabe M
Published: August 2014

Background: Emesis is one of the major non-hematologic toxicity caused by chemotherapy. The control of Chemotherapy Induced Nausea and Vomiting (CINV) is conducted to a life lengthening. Recently, CINV is controlled by the second generation 5-HT3 receptor blocker (Palonosetron; PALO) and a NK-1 receptor antagonist (Aprepitant; APR). It has been shown that dexamethasone (DEX) with 5-HT3 receptor blocker improves acute/delayed CINV. However, it has not been determined the medication schedule of DEX with PALO and APR. The purpose of this study is evaluated the efficiency of palonosetron, aprepitant and dexamethasone for day1 with or without dexamethasone on days2 and 3.

Methods: Breast cancer patients who administered anthracyclin drug regimen have been eligible from April, 2011 to June, 2012. The patients were randomised to group A (PALO/APR/DEX one day) and group B (PALO/APR/DEX three days). Eighty patients was estimate as study samples. The primary endpoint was a complete response (CR) rate of vomiting, the secondary endpoint was a complete control (CC) rate of vomiting.

Results: Forty patients were enrolled in this study, and patient recruitment is continued. CR rate was no significant difference in both groups (76.9% of group A, 73.3% of group B). CC rate of group A (61.5%) did not show inferiority compared with group B (40.0%).

Conclusions: In this current study, we suggest that one day dexamethasone treatment could reduce enough the emesis of high emetogenic chemotherapeutic agents.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-12-13.
Abstract P3-01-05: The Role of Mammographic Calcification in the Neo-adjuvant Therapy of Breast Cancer Imaging Evaluation
Authors: Li JJ , Chen CM , Di GH , Wu J , Lu JS , Shao Z-M
Published: August 2014

Aim: To evaluate the relationship between malignant appearance of mammographic calcification and breast cancer pathological features, and to explore the predictive value of calcification appearances and morphology changes in neo-adjuvant setting.

Methods: 419 patients with operable breast cancer received neo-adjuvant therapy between 2008.2 and 2011.8 in Shanghai Cancer Hospital. Core needle biopsy was conducted before preoperative therapy to determine cancer and achieve pathological features. Mammogram (MG), ultrasound and breast MRI were routinely done prior to therapy and prior to surgical operation. We conducted a detailed analysis of MG images in patients with malignant calcification, recorded the morphology, distribution, range, density, diameter and number of the calcification.

Results: 419 patients enrolled, 108 patients (25.8%) showed malignant calcification in MG, 6 patients missed the first MG before therapy. 214 patients were Luminal A, 95 were Luminal B, 64 were Her2 positive and 46 were triple negative, the pCR rate was 14%, 30.5%, 53%, 43.5% respectively. Patients with malignant calcification have more ER positive (81.5% vs. 71.7%, p = 0.045) and HER2 positive (51.8% vs. 33%, p = 0.001) diseases. The pCR rate was 26% in patients with malignant calcification and 28% in patients without, p = 0.8.

Different morphology shapes showed similar pCR rate, p = 0.89. Casting-type had a higher pCR rate 45.8%, compared with 20% in crushed stone-like and 16.7% in powderish, p = 0.031. Range more than 5cm had a higher pCR rate, 40.7% vs. 20%, p = 0.034. Density, diameter and number of the calcification did not reach statistical difference, however high density, diameter >1mm and number >20 per cm2 showed a trend of higher pCR rate. Patients with diameter ≤0.5mm had a higher lymphatic vascular invasive rate 51.4%, compared to diameter≤1mm (26.8%) and diameter >1mm (22.7%), p = 0.03. Morphology and distribution of calcification did not change obviously. Less than 30% patients showed changes in range, number or density, no relationship with pCR rate.

Conclusion: Patients with malignant calcification are more likely to have ER positive and Her2 positive diseases. MG should be considered the standard prior to the start of therapy, the distribution and range of the calcification may predict pCR rate. Calcification appearance does not change significantly after neo-adjuvant therapy, therefore MG is not an appropriate method for efficacy evaluation. But MG before surgery is still useful to identify the extent of surgery, especially in breast conserve therapy.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-01-05.
Abstract P3-01-06: Ultrasound as single mode of imaging may miss significant pathology in symptomatic women aged 35–39
Authors: Baker EL , Masudi T , Waterworth A
Published: August 2014

Recent guidelines in the UK stipulate that symptomatic women aged under 40 with clinically benign disease do not need mammography as a standard part of their assessment.1 Previous practice at the Calderdale and Huddersfield NHS Trust has been to perform mammography on all women over 35 years old. This study was undertaken to determine if there would be an increase in false negative assessment under the new guidelines.

All female patients 35–39 years old attending symptomatic breast clinic with benign clinical examination and undergoing both ultrasound and mammogram evaluation were eligible. Patients with previous breast cancer or a clinically suspicious lump mandating mammography were excluded. The information was gathered retrospectively using patient records. 96 women were included. Mammography and ultrasound results (including M and U valves) were compared for any discrepancy. If performed, biopsy results were also reviewed.

In 70% of patients there was no discrepancy between mammographic and ultrasonic evaluation (M = U). In 25% U score was one higher than M score. On further analysis this group mainly comprised of those with fibroadenomas or fibrocystic breast changes seen on ultrasound (U2) with a normal mammogram (M1).

In the remaining 5%, 3 patients had U score 2 greater than M score, 1 had M>U by 1 and 1 had M>U by 2. On further analysis of these discrepancies most patients had benign disease. In two patients with U5 scores and lower M scores malignancy was confirmed on biopsy. In one patient ultrasound showed benign disease (U2) but mammogram demonstrated suspicious calcifications (M4) that were confirmed as high grade DCIS on stereo-core biopsy.

In conclusion for the vast majority of patients in this group mammography does not add to the evaluation on presentation at symptomatic breast clinic. However this study identified a case (1 patient in 96) where significant disease could have been missed had a mammogram not been undertaken. The acceptable level of such false negative assessments with ultrasound only imaging in women under 40 must be further evaluated.

1Best practice diagnostic guidelines for patients presenting with breast symptoms Alexis M Willett, Michael J Michell, Martin J R Lee, November 2010

Printed by Breakthrough Breast Cancer, www.dh.gov.uk/publications

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-01-06.
Abstract P3-01-07: ESTIMATED RISK OF RADIATION-INDUCED BREAST CANCER FROM MAMMOGRAPHIC SCREENING
Authors: Freitas-Junior R , Correa RS , Peixoto J-E , Ferreira RS , Tanaka RMN
Published: August 2014

Objective: Estimate the benefit–risk balance of mammography, as number of lives saved/lost in an opportunistic screening in the state of Goiás, Brazil, in 2010, according to type of technology available and age group indicated for screening.

Methods: The number of lives saved was estimated considering the gross mortality rate for breast cancer, female population living in the state, estimated mortality rate reduction due to screening programs, and mammographic coverage in the state. For number of lives lost, the model adopted by the Biological Effects of Ionizing Radiation (BEIR VII) was used. Based on the mean glandular tissue dose (Dg), the following parameters were calculated: number of radiation-induced cancer cases with one exposure, with several exposures in screening programs and over the lifetime, number of deaths caused by radiation-induced cancer at a certain age and over the lifetime. Dg of each equipment was estimated according to the European protocol, using the incident air kerma (Ki) at the simulator entrance and the half-value layer (HVL) of the X-ray beam, and table values of coefficients to convert Ki into Dg. Ki and HVL were measured in 100 equipments in operation in the state. A standard breast simulator (5.3 cm thickness and 50% glandular tissue) was used. We considered a biannual mammographic screening with an exam routine composed of a cranio-caudal and a mediolateral oblique view and 40–70 and 50–70-year age groups.

Results: The mean Dg was 4.28 (±1.06) and 6.61 (±3.67) for conventional and digital equipments, respectively (p < 0.001). A woman undergoing mammography at the age of 40 in a conventional equipment has a 0.243/100000 probability of radiation-induced cancer at the age of 60, whereas using a digital equipment, the probability is 0.375/100000. The number of cases of radiation-induced breast cancer over the lifetime and consequent deaths followed the differences in the doses employed according to type of technology (p < 0.001). The balance between lives saved and lost was 75.5 (1253.8/16.6) and 166.5 (849.4/5.1) for women screened at 40–70 and 50–70 years, respectively.

Conclusions: Screening among 50–70-year-olds, performed biannually using conventional equipments, presented more benefits regarding radiation protection. The number of cases of radiation-induced breast cancer and consequent deaths reproduces the same ratio observed for the difference in the doses between the types of technology.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-01-07.
Abstract P3-01-08: Mammographic density and estrogen receptor α gene polymorphism in Javanese ethnic women
Authors: Choridah L , Aryandono T , Faisal A , Sadewa AH , Purnomosari D
Published: August 2014

Background: Mammography density reflects the number of stromal and epithelial and one of strongest risk of BC. Estrogen plays an important role in the occurrence of breast cancer through a mechanism of proliferation and genotoxic effects. Action of estrogen on breast tissue by binding to estrogen receptors. The main estrogen receptor α is coded as ESR1 gene. The most studied variants in this gene are the PvuII and XbaI polymorphisms, which have been associated to lower sensitivity to estrogen.

Objective: To determine the proportion of genetic variation ESR1 XbaI and PvuII in Javanese ethnic woman in Yogyakarta, Indonesia and to study the correlation between genetic variations in these genes with mammogram density based on quantitative methods. This reaserch to be used as preventive measures for the development of genetic marker breast cancer risk associated with the density of mammography for younger women who have not entered the age to undergo mammography and can be useful as a reference for evaluation of anti estrogen therapy.

Method: Conducted digitizer mammogram density assessment using quantitative rating system based on computer-assisted methods of measurement with cumulus program based on interactive thresholding. Polymorphism identification ESR1 XbaI and PvuII RFLP obtained through PCR process. The numbers of genotyped cases and controls for each marker were 50 cases and 58. Mean of density and frequencies of SNPs were compared between cases and controls to identify SNPs associated with cancer susceptibility. Using anova, independent t-test, cruskal wallis and mann whitney u test we calculated significant different between SNP genotype group.

Results: The mean of mammographic density is higher in cases (52%) than in controls (0,41%) (p < 0,05). Means of mammographic density were compared by ESR1 genotypes and haplotypes. The percentage density was higher in women with one or two copies of the PvuII p allele (means for CT/Pp and TT/pp are 49 % and 48 %, respectively) than in those with the CC/PP genotype (39%), TT VS CC (P >0,05). Women with one or two copies of the XbaI × allele had higher mean percentage density (AG/Xx and AA/xx, 49% and 47%, respectively) than those with the GG/XX genotype (32%,), AAVGG P < 0,05. Persentage of TT genotype and mean of density is higher in cases (30%, 52%) than controls (10,2%, 40%).

Conclusion: Haplotype 2 (TG/PX) was associated with lower sensitivity to estrogen and reflects as decrease of mammographic density. The findings of this study support the view that ESR1 polymorphisms may affect breast cancer risk through differences in breast density.

Keywords: Breast Cancer, Mammogram Digitizer, DNA polymorphism ESR 1 PvuII, ESR1 XbaI, PCR RFLP

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-01-08.
Abstract P3-02-05: Subtypes of screen-detected invasive breast cancer and symptomatic invasive breast cancer and their impact on survival
Authors: Kobayashi N , Hikichi M , Miyajima S , Utsumi T
Published: August 2014

Background: Breast cancer is a worldwide problem which urgently requires solution, in many countries still being the most common cause of malignancy associated death. The screening program aims to detect early breast cancer to improve survival. We investigated the clinicopathrogical characteristic including intrinsic subtypes and outcome of patients with screen-detected invasive breast cancer (S-DIBC) compared with those with symptomatic invasive breast cancer (SIBC).

Material and Methods: From January 2005 to December 2011 840 patients with invasive breast cancer who underwent surgery at our hospital were included. There were 195 S-DIBCs and 645 SIBCs. We retrospectively reviewed the clinical and pathologic data. Ki-67 LI was categorized as low (<14%) and high (> or = 15%). Tumors were classified into four groups based on the expression of ER, PgR, Ki-67 and HER2 as follows: luminal A (ER+ and/or PR+, and HER2− and Ki67 low), luminal B (ER+ and/or PR+, and HER2+ or Ki67 high), HER2 disease (ER−, PR−, HER2+), and triple negative (ER−, PR−, HER2−). Overall survival (OS) and relapse-free survival (RFS) curves were generated using the Kaplan- Meier method. Survival comparisons were made with the log-rank test, the level of significance was taken to be 0.05. SPSS 18.0 software package was used for statistical analysis.

Results: S-DIBC was associated with smaller tumor size, less lymph node involvement, and earlier stage compared with SIBC (P < 0.001). Significantly more tumors were positive for hormone receptors in the S-DIBC group as compared to the SIBC group (ER+,83.5% vs.75.1%, p = 0.017; PgR+, 73.4% vs. 60.6%, P = 0.009), with a greater proportion of the luminal A subtype in the S-DIBC group (S-DIBC: Luminal A 59.0%, Luminal B 25.6%, HER2 disease 4.6%, triple negative 10.8%; SIBC group: Luminal A 46.5%, Luminal B 30.0%, HER2 disease 6.6%, triple negative 16.8%). Patients with S-DIBC had better prognosis [5-year OS: 100% (S-DIBC) vs. 95.5% (SIBC), p = 0.005, 5-year RFS: 98.5 vs. 92.1%, p = 0.004]. Tumors detected with screening generally had more favorable outcomes than symptomatic cancers regardless of subtypes [5-year OS: (S-DIBC) Luminal A 100%, Luminal B 100%, HER2 disease 100%, triple negative 100%; (SIBC) Luminal A 95.9%, Luminal B 93.3%, HER2 disease 95.5%, triple negative 84.1%)].

Conclusions: Our results suggest that subtype distribution of S-DIBC differs from that of SIBC.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-02-05.
Abstract P3-02-06: Survival impact of early detection of recurrence after surgery in early breast cancer patients
Authors: Hojo T , Tamura K , Masuda N , Inoue K , Kinoshita T , Fujisawa T , Hara F , Saji S , Asaga S , Anan K , Yamamoto N , Wada N , Takahashi M , Nakagami K , Kuroi K , Iwata H
Published: August 2014

Background and Object: Annual mammography and physical examination as the follow-up tests after surgery were recommended to early breast cancer patients based on the two randomized clinical trials (GIVIO and Rosselli Del Turco) which were reported in 1990s. Whereas, radiological imaging and blood test (serum tumor marker) for early detection of recurrence are not recommended due to the lack of evidence from clinical trial. However, the imaging techniques (helical CT, bone scan, PET/CT. MRI et al) to detect minute lesions and therapeutic options for metastatic breast cancer have been remarkably advanced since then. In fact, routine radiological examinations after surgery were performed in several Japanese hospitals for aiming early detection of recurrence as the clinical practice.

We here evaluate the possible benefit of early detection of recurrence by radiological and laboratory examinations during post-operative follow-up period.

Methods: Clinical information of breast cancer patients who were diagnosed as recurrence after surgery during 2005–2006 was collected from 30 hospitals in Japan. Clinical and pathological characteristics such as molecular subtype of breast cancer, survival time from initial therapy or 1st recurrence, detection methods and symptomatic information when they diagnosed as metastasis were analyzed retrospectively.

Results: As the routine examination of post-operative follow-up, serum tumor maker, chest x-ray/CT, abdominal US/CT and bone scan were done in 95%, 57%, 38%, 24% of 30 hospitals, respectively. Of the 698 patients individually evaluated in this analysis, 248 had loco-regional recurrences and 450 had distant metastases. The first distant metastatic site were 35% in bone, 30% in lung, 17% in liver and 11% in lymph node, respectively. All individual patients are divided into symptomatic (45.7%) or asymptomatic groups (54.3%) at the detection of metastases. Asymptomatic metastases were detected by serum tumor marker (26%), bone scan (18%), chest x-ray (17%), chest CT (17%), abdominal US (11%) and abdominal CT (5%), respectively. The median disease-free interval (DFI) was 3.0 years in both groups, but the median survival time after the diagnosis of recurrence to death were 3.7 years in asymptomatic patients and 3.0 years in symptomatic patients, respectively. In addition, asymptomatic group had significantly superior overall survival (from primary surgery to death) than symptomatic group with oligo-metastases such as limited organ disease (P < 0.001).

Conclusions: Our data may support the hypothesis that early detection of breast cancer recurrences has beneficial impact on survival. Randomized clinical trial would be warranted to prove this hypothesis, and we are currently planning this.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-02-06.
Abstract P3-02-09: Cost-effectiveness of screening with additional MRI for women with familial risk for breast cancer without a genetic predisposition
Authors: Saadatmand S , Heijnsdijk EA , Rutgers EJ , Hoogerbrugge N , Oosterwijk JC , Tollenaar RA , Hooning M , Obdeijn I-M , de Koning HJ , Tilanus-Linthorst MM
Published: August 2014

Background: To reduce mortality risk, women with a family history of breast cancer are often screened with mammography before 50 years of age. Additional Magnetic Resonance Imaging (MRI) can improve sensitivity. MRI screening is cost-effective for BRCA1/2 mutation carriers. However, for women with a family history of breast cancer without a proven mutation cost-effectiveness is not clear. We evaluated the cost-effectiveness of additional MRI for women with a familial risk in the largest prospective MRI screening study: the Dutch MRI Screening Study (MRISC).

Materials & Methods: Between 1999 and 2007 a total of 1597 women (8370 women years at risk) between 25–70 years, with an estimated cumulative lifetime risk of 15–50% for breast cancer participated in the MRISC. Women were screened with clinical breast examination (CBE) every six months and annual mammography and MRI. We calculated the costs per detected breast cancer. In addition, MRISC data were incorporated into a micro simulation screening analysis model: MISCAN. This model simulates screening programs with different screening modalities and time intervals. Different screening schemes were evaluated and the cost per life-year gained (CLYG) estimated.

Results: Forty-seven breast cancers, including 9 Ductal Carcinoma in Situ, were detected. Screening with additional MRI leads to a cost per detected breast cancer treated of €101,962. In increasing age-cohorts the cost decreased, probably due to the higher breast cancer incidence. The cost per detected and treated breast cancer in age group 40–50 years doubled in the age group >60 years. We will demonstrate these results more extensively.

With MISCAN modeling we predicted that screening with this scheme from age 35 to 60 years reduces breast cancer mortality by 30% at a CLYG of €119,945 (3.5% discounting), compared to 21% estimated mortality reduction at €45,707 CLYG with mammography and CBE alone.

Conclusion: Screening with MRI may improve survival for women with familial risk for breast cancer, but is expensive. However, it may be cost-effective for a select group. We will discuss subgroups that may benefit from MRI screening and in which age category MRI was most effective in our study.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-02-09.
Abstract P3-03-02: The metastatic rate of IMLN, when IMLN metastasis is suspected with PET CT.
Authors: Lee J-H , Son G-T , Choi J-E , Kang S-H , Lee S-J
Published: August 2014

Background: Metastatic status of internal mammary lymph nodes (IMLNs) has a clinical importance in assessing stage and prognosis of breast cancer. But, when metastasis of IMLN is suspected, the management is controversial. We reviewed 29 breast cancer patients who had IMLN dissection, retrospectively, and investigated the pathologic status of IMLNs.

Methods: From August 2005 to December 2011, at Yeungnam University Hospital, 43 patients underwent IMLN biopsy or dissection for suspected IMLN metastasis on lymphoscintigraphy (7 patients), breast ultrasound (1 patient) or PET CT (29 patients), when diagnosed with primary or recurred breast cancer. 6 patients who had stage IV at diagnosis or had too obscure data to identify exact location of IMLN, were excluded. Among them, we reviewed clinicopathologic features of IMLN detected on PET CT and metastatic status of IMLNs was investigated.

Results: Total 29 patients were included in this study. 19 patients and 10 patients underwent IMLN dissection when diagnosed with primary or recurred breast cancer, respectively. Unlike conventional IMLN dissections, our IMLN biopsy or dissection was done during Radical mastectomy (in 2 pts.), modified radical mastectomy (in 14 pts.), using incision of breast conserving surgery (in 3 pts.) and separated incision (in 10 pts.), with or without resection of ribs.

The mean number of IMLNs was 2.76±2.15 and total metastatic rate of IMLN was 72.4% (21/29). The sensitivity, specificity, positive predictive value, and negative predictive value of PET CT was following: 91.3%, 42.8%, 72.4% and 27.6%. Mean standard uptake value (SUV) of metastatic and non-metastatic IMLN were 3.6±2.9 and 3.9±2.6 and there was no statistical difference (p-value=0.821).

During IMLN dissection, besides initial approach intercostals space (ICS), some metastatic IMLN was also found in upper or lower level ICS (42.9%, 6/14). Only IMLN metastasis without axillary nodes metastasis were found in 3 patients and the tumor location of these patients was all inner or central quadrant. Chest X-ray was done postoperatively as routine procedure, and there were no other specific complications such as pneumothorax or hemothorax.

Conclusion: IMLN dissection without radical mastectomy can be done safely without complications due to recent advance in diagnostic and surgical skills. If SUV on IMLN is shown on the PET-CT, IMLN dissection is needed, regardless of SUV. If breast cancer is located at inner quadrant, more aggressive dissection of IMLN is needed. Further follow-up and studies are needed to assess locoregional recurrence and to compare improvement in overall survival and disease free survival.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-03-02.
Abstract P3-05-02: Pathological assessment of discordant cases for molecular (BluePrint and MammaPrint) versus clinical subtypes for breast cancer among 621 patients from the EORTC 10041/BIG 3–04 (MINDACT) trial
Authors: Viale G , Slaets L , de Snoo F , van't Veer L , Rutgers E , Piccart M , Bogaerts J , van den Akker J , Stork-Sloots L , Engelen K , Russo L , Dell'Orto P , Cardoso F
Published: August 2014

Background: Biology has become the main driver of breast cancer therapy. Intrinsic biological subtypes by gene expression profiling have been identified. Pathology can be used to define surrogates of these subtypes but these are not always concordant, which may lead to different treatment plans. We investigated the concordance between BluePrint and MammaPrint (microarray-based) breast cancer subtypes and pathological surrogates (based on ER, PR, HER2 & Ki67).

Methods: Using available data (centrally assessed pathology and genomics) from the MINDACT pilot phase [Rutgers et al. EJC 2011] 621 tumors were analyzed. Patients were classified according to 4-category based pathology (ER, PR, HER2 and Ki67); additionally, classification was performed adhering to the recent St. Gallen recommendations [Goldhirsch et al. 2011], which recognizes an additional category (Luminal B HER2+). Based on BluePrint and MammaPrint 4 subtypes are formed: Luminal A (Luminal-type/MammaPrint Low Risk); Luminal B (Luminal-type/MammaPrint High Risk); HER2-type; and Basal-type. This study is an analysis of discordant patient groups (i.e. clinical HER2+/BluePrint Luminal-type; clinical Hormone Receptor (HR)-positive/BluePrint Basal-type) providing comparison of centrally assessed tumor heterogeneity as well as comparison of quantified ER, PR and HER2 results.

Results: Ki67 is often used as biomarker to distinguish Luminal A from Luminal B subgroups. The concordance between MammaPrint and centrally assessed Ki67 in Luminal-type patients is 71%, with a κ score of 0.35 (95% CI 0.26–0.45) indicating that Ki67 and MammaPrint cannot reliably substitute for each other. There is a relatively large group of clinical HER2+ cases that are BluePrint Luminal-type (29 out of 76; 38%) indicating that tumor expression of the Luminal profile is dominant compared with expression of the HER2 profile. These patients have high IHC ER results and fall into the group that St Gallen separately defines as Luminal B HER2-type. These patients may have lower response to trastuzumab [von Minckwitz et al. JCO 2012]. 12 out of 76 BluePrint Basal-type patients are clinical HR+. These patients have low centrally assessed IHC ER and PR expression (≥1% and <10%).

Conclusions: Marked differences are observed between BluePrint and MammaPrint (microarray based) breast cancer subtypes and centrally re-assessed pathological surrogates (based on ER, PR, HER2 & Ki67). The greatest discordance is seen in the sub-stratification of Luminal patients, and in the HR+/HER2+ patients. The observed subtype discrepancies may have an important impact on treatment decision making.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-05-02.
Abstract P3-06-16: Predictive biomarker of pathologic complete response to neoadjuvant chemotherapy in triple negative breast cancer
Authors: Kim T , Han W , Moon H-G , Noh D-Y
Published: August 2014

Neoadjuvant chemotherapy has been considered valuable beyond its role in facilitating conservative surgery and improving prognosis associated with pathologic complete response. Predictive factors of response would help to assess the expected individual benefit of this treatment. Bcl-2 and p53 have been mostly investigated predictive biomarker for the efficacy of chemotherapy in breast cancer, however, studies documenting predictive significance of biomarkers in triple negative breast cancer(TNBC) are limited by low n values of patients. Furthermore, studies did not provide consistent result to conclude about predictive value of biomarkers. There is no unique explanation to date to account for such inconsistencies across studies. In the present study, the two most studied inhibitors of apoptosis, the bcl-2 and p53, have been evaluated to assess whether they may play a role in modulating response to triple negative breast cancer to neoadjuvant chemotherapy. From January 2003 to December 2011, 187 patients presenting T1-4 N0-3 M0 primary TNBC were submitted to two different chemotherapeutic regimens before surgery. The first 154 received the doxetaxel/doxorubicin regimen, the remaining 33 were submitted to doxorubicin and cyclophosphamide followed by doxetaxel. The expression of p53, bcl-2 was evaluated in TNBC specimens obtained at diagnosis by core needle biopsy and at postchemotherapy surgery. Overall pathologic complete response(pCR) occurred in 43 of the 187 cases(23%). The pCR rate was superimposable in the patient subgroups with bcl-2-positive or –negative primary tumors. Conversely, p53 expression was significantly associated with higher pCR rate(19.5 vs 73.2%; p = 0.026; in patients with p53- and p53+ breast cancer). In a multivariate regression analysis, after adjusting for tumor and node status, treatment administered, p53 status maintained an independent predictive role for pCR.[relative risk(RR)=6.247, 95% confidence interval (CI)=0.9–39.1] In our homogeneous patient population, pCR was not associated with initial clinical stage, nodal status as well as other clinicopathologic factors. The status of the p53, which is mutated in a high percentage of breast tumors, is a predictive factor for cytotoxic drug activity. By contrast, bcl-2 failed to be related to chemotherapy activity.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-06-16.
Abstract P3-06-29: Change of circulating tumor cells before and after neoadjuvant chemotherapy in patients with primary breast cancer
Authors: Horiguchi J , Takata D , Rokutanda N , Nagaoka R , Tokiniwa H , Tozuka K , Sato A , Kikuchi M , Oyama T , Takeyoshi I
Published: August 2014

Background: Circulating tumor cells (CTCs) in peripheral blood may represent the possible presence of early tumor dissemination. However, relatively few studies were designed to investigate the change of CTC status by adjuvant chemotherapy in operable breast cancer patients.

Patients and methods: Peripheral blood (7.5ml) was collected from 95 patients with stage II/III breast cancer before neoadjuvant chemotherapy (NAC). NAC consisted of anthracycline and paclitaxel chemotherapy and additional trastuzumab treatment for patients with HER2-positive tumors.

Results: The average age of patients was 52.6 year old (median 52.0). One or more CTCs were detected in 18 (18.9%) of 95 patients. CTCs were detected in 6 (12.0%) of 50 patients with clinical stage II disease and 12 (26.7%) of 45 patients with clinical stage III disease. According to tumor subtypes, CTCs were detected in 5 (17.9%) of 28 patients with hormone receptor (HR)-positive and HER2-negative tumors (L subtype), 3 (12.5%) of 24 patients with HR-positive and HER2-positive tumors (L-H subtype), 4 (22.2%) of 18 patients with HR-negative and HER2-positive tumors (H subtype), and 6 (24.0%) of 25 patients with HR-negative and HER2-negative tumors (TN subtype). After NAC, 17 (94.4%) of 18 patients who were CTC-positive before chemotherapy changed into negative status. 30 (31.6%) of 95 patients had a pathologic complete response (pCR) after NAC. There was no correlation between CTC status before NAC and pathological response. At the median follow up of 27 months, distant metastasis was observed in 9 patients (9.5%). Patients with clinical stage III, TN subtype, or non-pCR had a significantly worse disease-free survival (DFS). However, CTC status before NAC was not a significant prognostic factor.

Conclusion: NAC has a significant impact on CTC status irrespective of tumor subtypes. CTC status before NAC was not a significant prognostic factor in this study. The reason of which may be that most of patients showing positive for CTCs before NAC have changed into negative after NAC.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-06-29.
Abstract P3-06-33: Effect of trastuzumab-based therapy on serum activin A levels in metastatic breast cancer.
Authors: Zubritsky LM , Ali SM , Leitzel K , Koestler W , Fuchs E-M , Costa L , Knight R , Laadem A , Sherman ML , Lipton A
Published: August 2014

Background: Only half of HER2-positive metastatic breast cancer patients will respond to first-line trastuzumab-containing therapy, but of these, most will progress within a year. Trastuzumab resistance remains a continuing clinical problem, and better biomarkers and therapies are needed. Activin A is a TGF-beta superfamily member that regulates cell proliferation, apoptosis, differentiation, and immune response. We have previously reported that higher pretreatment serum activin A level predicted reduced progression-free survival (PFS) and overall survival (OS) to first-line trastuzumab, independent of age, line of therapy, CA 15–3, and hormone receptor status (ASCO Ab ID 607, 2012).

Methods: Serum activin A was measured using ELISA (R&D Systems, Minneapolis, MN) in 60 metastatic breast cancer patients before and 1 month after starting first-line trastuzumab-containing therapy. PFS and OS were analyzed using the Kaplan-Meier method and Cox modeling with both continuous and dichotomous (median) serum activin A analyses.

Results: Pretreatment serum activin A levels had a median of 629 pg/mL and an inter-quartile range of 406 to 1791 pg/mL. There was no significant change in activin A levels between pretreatment and one month after starting trastuzumab therapy. Median activin A level at one month was 655 pg/mL, with an inter-quartile range of 405 to 1517 pg/mL. 83% of patients who had low pretreatment activin A levels (below median) had low activin levels at one month, and 83% who had high activin levels (above median) at baseline had high activin A levels at one month. Patients who had high activin A levels at baseline and one month had the worst outcome for both PFS (HR 3.9; median 134 days vs.776 days; p < 0.0001) and OS (HR 6.7; p < 0.0001) when compared to patients with low activin A levels which remained low at one month.

Conclusions: Higher pretreatment and 1 month post-treatment serum activin A predicted for reduced PFS and overall survival in metastatic breast cancer patients treated with first-line trastuzumab-containing therapy. Trastuzumab-based therapy did not have a significant effect on activin A levels at one month. Patients with persistently high activin A levels had significantly worsened outcomes compared to those with low activin A levels. Serum activin A deserves further study to select patients most likely to respond to activin A-targeted therapy.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-06-33.
Abstract P3-07-07: Incidence and survival among breast cancer patients in the United States by race and stage diagnosis: an analysis of national registry data 2000–2009
Authors: Lang K , Huang H , Namjoshi M , Federico V , Menzin J
Published: August 2014

BACKGROUND: This study evaluated incidence and survival among breast cancer (BC) patients in the United States during 2000–2009, by race and stage at diagnosis.

METHODS: The Surveillance, Epidemiology, and End Results (SEER) Program SEER*Stat Database was used for this analysis. SEER is an epidemiologic surveillance system consisting of population-based tumor registries designed to track cancer incidence and survival in the US. The registries routinely collect information on incident cancer cases in areas that represent approximately 25% of the US population. We evaluated age-adjusted (to the 2000 US standard population) incidence (number of cases per 100,000 population), and 1- and 5-year survival among newly diagnosed female breast cancer patients during 2000–2009, by cancer stage (localized, regional, distant and unknown/unstaged) and race (White, Black, Other [American Indians/Alaska Natives or Asians/Pacific Islanders]).

RESULTS: A total of 543,539 cases of female BC were reported to SEER during 2000–2009, with 452,047 cases among Whites (W), 54,310 cases among Blacks (B), and 37,182 among other races (O). The overall incidence was highest for Whites (130.2 per 100,000 population), followed by Blacks (120.1) and other races (59.6–93.2). Similarly, incidence of localized BC was highest among Whites (81.1), followed by Blacks (63.0) and other races (35.4–58.7). Blacks had the highest incidence of regional (43.6 vs. 18.8–40.1), distant (9.7 vs. 3.7–6.0), and unknown stage of BC (3.8 vs. 1.6–3.0) compared to Whites and other races. Incidence of localized BC decreased slightly for Whites (average annual change −0.4%) during 2000–2009; however it increased for all other groups (1.4–1.8%). Incidence of distant BC increased for all races (W: 1.0%, B: 2.3%, O: 3.1–3.8%). Blacks had the lowest one-year and five-year survival for localized, regional and distant BC.

One-year and five-year survival rates were relatively stable during 2000–2009 for regional and localized BC (annual average change: −0.6% to 0.7%), for all races. For distant BC, Blacks had least improvement during 2000–2009 in one-year survival (annual average change 0.03%, vs. 0.6% for Whites and 3.6% for other races), and decreasing five-year survival (annual average change −5.4% vs. 2.2% for Whites and 1.7% for other races).

CONCLUSIONS: Based on US population-based registry data, Blacks had higher incidence of more advanced breast cancer and lower long-term survival for all stages of BC. There is considerable room to improve survival rates for patients with regional and distant BC, especially among Blacks. Further studies evaluating the survival experience of later-stage BC patients based on other key factors, such as age, socioeconomic status, treatment patterns, and tumor characteristics (e.g. ER/HER2 status) are warranted.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-07-07.
Abstract P3-07-11: Retrospective database review of outcomes in invasive lobular carcinoma and invasive ductal carcinoma of the breast
Authors: Shih Y-C , Dillon P
Published: August 2014

Background. Invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) are histologically distinct breast cancer subtypes. While ILC and IDC have similar disease-free survival (DFS) and overall survival (OS), the patterns of metastatic recurrence are suspected to differ due to differing adhesion markers.

Methods. Retrospective review of a cohort of breast cancer patients treated at a tertiary academic medical center from May 1999 to April 2012 was performed. Demographic, pathologic, treatment and follow-up data were collected from a cancer database and the institutional medical records.

Results. There were 179 ILC and 358 IDC (1:2 stage-matched) patients in the study period. Mean age (59 vs. 58 years), gender, race (88% vs. 80% Caucasian), menopause state (71% vs. 66% post-menopausal), and family history (48% vs. 42% positive for breast cancer) were similar in the two groups. Median follow-up was 4.7 years. ILC patients had more negative mammograms upon diagnosis (6.8% vs. 1.4%, p = 0.001), and their breast cancers were more likely to be hormone-receptor-positive/HER2-negative (90% vs. 69%, p < 0.00001). The recurrence rate was the same between ILC and IDC. ILC recurred more often in the abdominal cavity (24.3% vs. 4.1%, p = 0.001), and it recurred similarly to IDC in other sites (bone, lung, liver, central nervous system, and local). Both groups received similar treatments, including number of surgical resections (1.3), positive margins (17%), breast-conservation rate (42% in ILC vs. 49% in IDC), systemic treatment (91% vs. 88%), and taxane use during chemotherapy (71% vs. 69%). The DFS (10.6 vs. 11.4 years), OS (10.2 vs. 11.9 years), and breast-cancer-specific OS (11 vs. 13 years) were not statistically different. In a subgroup analysis, stage IV ILC patients had worse overall survival than stage IV IDC patients (2.9 vs. 6.8 years, p = 0.039). On multivariate analysis, age, stage of disease, hormone receptor status, and systemic therapy were associated with survival, but histology was not.

Conclusions. Compared to ductal breast cancers, lobular breast cancers recur more often in the abdominal cavity. Both ILC and IDC have comparable surgical and medical treatment outcomes, including resection number, positive margin of resection, breast conservation rate, recurrence rate, and survival.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-07-11.