bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of exemestane on bone mineral density in postmenopausal women at increased risk for breast cancer.
Authors: Eng-Wong J , Reynolds JC , Venzon D , Wedam S , Prindiville S , Zujewski J , Korde L
Published: December 2010

Abstract #5086

Background: The aromatase inhibitors (AIs) show promise for breast cancer prevention in postmenopausal women. However these agents have been shown to decrease bone mineral density in women with breast cancer. Exemestane, a steroidal aromatase inhibitor, may be more bone sparing than the non-steroidal aromatase inhibitors.  Methods: We conducted a phase II trial of exemestane in postmenopausal women at increased risk of breast cancer to assess the effect on anterior-posterior (AP) spine and total hip bone mineral density (BMD). Eligible participants are at increased risk for breast cancer by virtue of: Gail model risk > 1.7% over 5 years; high risk pathological lesion (e.g. lobular neoplasia, ductal carcinoma in situ); known BRCA1/2 deleterious mutation or prior stage I/II breast cancer at least 2 years from breast cancer treatment and not treated with AIs. Women were required to undergo DEXA scan of the AP spine and hip at baseline and were excluded if AP spine T-score was ≤-2.5. AP spine measurements were done twice at each time point and the results averaged. Study participants receive exemestane 25 mg, calcium carbonate 1200 mg and vitamin D 400 IU daily for two years. We report the results of a planned interim safety analysis assessing one year change in bone density in the first 18 subjects. Student's t-test was used to determine relative change from baseline in AP spine and total hip BMD.  Results: To date, 30 women have enrolled in the trial and 21 have completed 1 year of exemestane. Three women discontinued agent after an average of 3 months due to joint pain. For the 21 included in this analysis 15 were eligible due to a high risk pathological lesion, 4 by Gail Model and 2 by prior breast cancers. The average change in AP spine BMD from baseline to 1 year (N= 21) is –1.3 %, range -10.0 to +7.0% (p=0.20 for the null hypothesis of zero overall change; 95% C.I. for the mean -3.2% to +0.7%). Average AP spine T score is -0.28 at baseline and -0.45 at one year. Change in total hip BMD is -1.4%, range -7.5% to 5.9% (p=0.058, 95% C.I. -2.8% to +0.1%). Average total hip T score is -0.05 at baseline and -0.17 at one year.  Conclusions: These preliminary data suggest that exemestane 25 mg/day for one year with concurrent calcium and vitamin D has acceptable effects on bone density in postmenopausal high risk women, although there were wide ranges in effects. The observed average reduction in BMD is less than the reported effect in treatment studies of women with invasive breast cancer. Studies are in progress to determine whether exemestane use by postmenopausal women is effective in reducing the risk of invasive breast cancer.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5086.
Hormone therapy – who takes it – the rich or the poor?.
Authors: Massey EJ , Chaudhry A , Thomas R , Robert P , James B , Charlie C
Published: December 2010

Abstract #5093

Introduction: In the UK, hormone therapy is provided to all breast cancer patients for a standard NHS prescription charge (approximately USD13 per month). Previous studies in the USA and the UK have shown that only 60% of patients comply fully with prescribed therapy. This study examines the effects of age, drug type, prognosis and social deprivation on hormone therapy compliance.  Method: During scheduled outpatient appointments data was collected from patients as part of their routine follow-up. Parameters included: age, name of drug, time on drug, drug compliance (full; deviation – missing <1 pill/week; holiday – missing pills > 1 week; stopped), and side effects (subjective – mild; moderate; severe). Prognostic information was derived using the Nottingham Prognostic Index (NPI). The patients' home postal codes were collected and allocated to the correct electoral ward (small geographical areas with average population of 5500). Using data from the UK National Census in 2000, information on social status was derived from the patients' postal codes and given as the Index of Multiple Deprivation (ID2000). The ID2000 has both an ID2000 score and ID2000 ranking (1 to 8414) for different electoral wards across England & Wales. Low ID2000 scores and high ID2000 rankings correspond to areas of affluence. Patients in ID2000 rankings <4212 were assigned as 'deprived' and >4212 as 'affluent'. The predominant social grade for each ward was recorded (AB, C1, C2, D and E).  Results: To date, 117 patients have been analysed. The ID2000 ranks ranged from 1033 to 8297. Ninety two (89%) of patients were fully compliant, 5 (5%) deviated, 2 (2%) took a holiday and 4 (4%) stopped taking their hormone treatment. Compliance was significantly better for those taking an aromatase inhibitor (AI) (96.7%) than tamoxifen (80.5%) (Chi2 test Chi2 = 7.147. p = 0.0075). Compliance is unaffected by affluence (92.5%) v deprivation (80.9%) (Chi2 test Chi2 = 2.486, p=0.11). Compliance is also unaffected by NPI (Mann Whitney U test p=0.84) and age (Mann Whitney U test p=0.78).  Conclusion: These early data suggest that hormone drug compliance in our centre is higher than previously reported. Compliance is significantly higher for aromatase inhibitors than tamoxifen; currently there is no discernable difference between individual AIs. Compliance appears higher in affluent patients; however this is not statistically significant. Compliance appears to be independent of age, duration of therapy and prognosis. This study is ongoing and further work comparing different areas is recommended.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5093.
Choosing breast reconstruction – for richer, for poorer?.
Authors: Roe T , Massey E , Chaudhry A , Price R , Chan C
Published: December 2010

Abstract #5094

OBJECTIVE  To assess whether the age or socio-economic status of patients undergoing mastectomy play any part in influencing their decision to undergo breast reconstruction.  METHODS  Details were collated from all patients undergoing mastectomy with or without reconstruction under the care of a single surgeon at Cheltenham General Hospital over a 5 year period. All patients having a mastectomy were offered a reconstruction. Zip codes were used to assign government deprivation scores and the corresponding national rank for each patient's residential district, according to the 2000 UK national census. Affluent areas have low scores and high rank; deprived areas have high scores and low rank. The Mann-Whitney U test was used to determine whether there was a statistical difference in age or social status between those patients in the mastectomy only group and those who were reconstructed.  RESULTS  50 patients underwent mastectomy only (median age 63.5, IQR 52-72), 30 opted for reconstruction (median age 53.5, IQR 44.5-58). There was a statistically significant difference (at the 95% confidence interval) between the average age of the 2 groups (P=0.0002).  Median deprivation score for the mastectomy group was 10.4 (6.28-17.84) and for the reconstruction group 9.67 (6.52-17.37). This was not significant (P=0.26).  Median ranks were 6224 (4008-7525) and 6511 (2502-7213) respectively (P=0.29).  CONCLUSIONS  The socio-economic status of patients does not affect their decision on whether or not to undergo post-mastectomy reconstruction. However, younger patients are statistically more likely to opt for a reconstructive procedure.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5094.
Racial disparities in breast cancer knowledge.
Authors: Petrak GA
Published: December 2010

Abstract #5099

Background: Many women fear breast cancer, but may know a great deal about the disease. We assessed the breast cancer attitudes and knowledge of women who self-identified as Caucasian, African American, Asian American, and Hispanic/Other.  Methods: We created a survey to measure women's attitudes and knowledge regarding breast cancer. We surveyed women outside retail establishments in Michigan and Washington, DC. We obtained 160 responses. We analyzed the data using the students t-test for continuous variables and the chi-square test for categorical variables, with significance set at the 0.05 level.  Results: The racal distribution was: Caucasian, N = 119 (74.4%); African American, N = 19 (12%); Asian American, N = 17 (11%); other, 4 (2.5%), one respondant did not state her race. We asked: (1) Have you ever had a mammogram? Caucasian, No = 38 (32%); African American, No = 6 (33%); Asian American, No = 13 (76%): P=0.007. (2) True/False: A mammogram does not use radiation to image the breast. Caucasian, False = 72 (64%); African American, False = 13 (76%); Asian American, False = 9 (56%): P = 0.07. (3) True/False: All women with breast cancer need chemotherapy. Caucasian, False = 88 (93%); African American, False = 11 (92%); Asian American, False = 10 (77%): P = 0.03. (4) True/False: All women who need chemotherapy receive it. Caucasian, False = 88 (93%); African American, False = 11 (92%); Asian American, False = 10 (77%): P = 0.04.  Discussion: Caucasians and African Americans were very similar in their breast cancer knowledge, but Asian Americans were less likely to have had a mammogram, less likely to know about radiation and mammograms, less likely to believe that all women with breast cancer need chemotherapy, and more skeptical regarding whether women who need chemotherapy actually receive it.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5099.
The UK NIHR multicentre randomised COMICE trial of MRI planning for breast conserving treatment for breast cancer.
Authors: Drew PJ , Harvey I , Hanby A , Brown S , Olivier C , Napp V , Brown J , Turnbull LW , Trialists on Behalf of Comice
Published: December 2010

Abstract #51

The role of the addition of MR imaging (MRI) to routine techniques for loco-regional staging of primary breast cancer is unclear. The UK NIHR HTA multicentre COMICE trial considered whether adding an MRI scan to conventional triple assessment (mammogram, ultrasound and biopsy) assisted loco-regional staging and thereby reduced re-operation rates, for patients with primary breast cancer scheduled for wide local excision.  The primary endpoint of the COMICE trial considered the proportion of patients undergoing a repeat operation or mastectomy at further surgery within six months of randomisation, or an avoidable mastectomy at initial surgery (re-operation rate). This was compared using logistic regression adjusting for age, breast density, and surgeon.  Between December 2001 and January 2007 1625 patients were randomised to receive MRI (817) or not (808). Re-operation rate within six months (primary outcome) was 18.8% (MRI) and 19.3% (no MRI). No significant difference between the arms was detected (odds ratio=0.96, 95% CI=[0.75, 1.24], p=0.7691). Secondary endpoints included quality of life, imaging effectiveness and local recurrence.  The results of the COMICE trial indicate no significant benefit in terms of reduction in re-operation rates, by the addition of MRI to conventional triple assessment for this patient group. These results have importance from both health economic and patient burden perspectives.  This project was funded by the NIHR Health Technology Assessment (HTA) Programme (project number 99/27/05) and will be published in full in an HTA report.The view and opinions expressed therein are those of the authors and do not necessarily reflect those of the UK Department of Health.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 51.
Racial disparities in magazine coverage of mammography.
Authors: Petrak GA
Published: December 2010

Abstract #5100

Background: African-American (AA) women are diagnosed with breast cancer later, at a higher stage disease, and have a higher mortality than European-American (EA) women. AA women have a lower rate of mammography screening and this lower rate may account, in part, for AA women's more severe disease at diagnosis and higher mortality. One possible reason for this racial disparity in mammography screening may be that AA women receive a different message than EA women from mass circulation magazines about mammography.  Material and Methods: A computer-aided content analysis was performed of AA and EA women's magazines with a circulation of greater than one million that contained at least 1,000 words across all the mammography-related articles or sections of articles that were published between January 1, 2002 and December 31, 2007. The words that shared similar meanings were grouped into seven categories: (1) religiosity, (2) activity, (3) positive and (4) negative emotions, (5) medical terms, (6) risk factors, (7) race portrayed, by which is meant when race was noted in articles as African American/Black or European American/White. The frequencies of each word were counted across all articles by type of magazine, i.e., predominately AA readers and EA readers. The Pearson product-moment method was used to calculate correlations, the Student's t-test was used for correlated samples to compare the means of the continuous variables, and McNemar's test was used to assess the difference between two correlated proportions. Significance was set at the 0.05 level.  Results: The magazines that met the study criteria were the African-American magazines Ebony and Essence and the European-American magazines Good Housekeeping, Marie Claire, Redbook, and Vogue. The six magazines yielded the following total number of words per magazine that focused on mammography: (a) Ebony: 17,221 words, (b) Essence: 20,257 words, (c) Good Housekeeping: 12,998 words, (d) Marie Claire: 7,654 words, (e) Redbook: 29,201 words, and (f) Vogue: 11,482 words. The word categories were compared in terms of their relative word frequencies, AA and EA.    Discussion: There were clear differences in the mammography messages presented in the AA and the EA magazines. The AA magazines contained more references to religiosity, activity, positive and negative emotions, and risk. It was striking that racial references to African Americans were ubiquitous in the African-American magazines, whereas, racial references to either African Americans or European Americans were almost completely absent from the European-American magazines.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5100.
Clinical impact of pathological axillary downstaging in locally advanced breast cancer after primary systemic chemotherapy.
Authors: Zambetti M , Bianchini G , Bianchi G , Mariani G , Moliterni A , Mariani P , De Benedictis E , Valagussa P , Greco M , Gianni L
Published: December 2010

Abstract #5103

Background Primary Systemic Chemotherapy (PSC) can result in pathologic axillary downstaging even in Locally Advanced Breast Cancer (LABC), which is generally associated with unfavorable prognosis and high incidence of nodal metastases. Aims were to evaluate: the clinical and biological factors associated with the likelihood of obtaining negative pathological nodes (pN0); the relationship between outcome and axillary nodal status at diagnosis (cN) and at surgery after PSC (pN).  Methods Women with LABC consecutively treated at the Istituto Nazionale Tumori in Milan from 1991 to 2007 were evaluated. Patients received PSC containing Doxorubicin ± Paclitaxel (+ adjuvant or neoadjuvant CMF) and endocrine therapy ± trastuzumab. Fixed right-censoring at 5 years was performed. Associations with Disease-Free Survival (DFS) and Overall Survival (OS) were evaluated using Kaplan-Meier (log-rank test) and Cox regression analysis. All confidence intervals are at 95%.  Results 451 women submitted to surgery and complementary RT were included in the analysis. 68% of surviving patients were followed for at least 5 yrs. 5y-DFS and OS were 51% (46-57%) and 70% (65-75%) respectively. ER negative, PGR negative, high grade and age <50 yrs were correlated with likelihood of pN0 at univariate logistic analysis, while ER negative only (OR 3.49, CI 1.65-7.66; p=0.001) retained significant role in the multivariate analysis.  Relationship between axillary status and outcome are shown in table 1.    Multivariate Cox regression analysis showed that positive nodes at diagnosis (HR 2.13, CI 1.07-4.22; p=0.03) and at surgery (2.84, CI 1.77-4.56; p<0.001), negative PGR (HR 1.79, CI 1.12-2.86; p=0.01), inflammatory status (HR 1.51, 1.02-2.23; p=0.04) and age < 50 yrs (HR 2.23, CI 1.58-3.16; p<0.001) were independent predictors of DFS. Multivariate analysis for OS demonstrated positive nodes at surgery (HR 3.46, 1.80-6.67; p<0.001), negative PGR (HR 2.21, CI 1.16-4.20; p=0.01) and age < 50 yrs (HR 2.00, CI 1.26-3.17; p=0.003) as significant variables. Pathologic complete response in breast was not significant in both multivariate analysis.  Conclusions Axillary downstaging was obtained in a significant proportion of patients with LABC. pN0 status after PSC identifies a clinical subgroup with better prognosis irrespectively of locally advanced disease and, in this subgroup of patients, it is a prognostic factor stronger than pathologic complete response in the breast.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5103.
Remarkable complete pathologic response rate after preoperative paclitaxel, gemcitabine, and trastuzumab chemotherapy in HER2 positive stage II/III breast cancer: a phase II multicenter study.
Authors: Im S , Lee K , Lee E , Kwon Y , Noh D , Park I , Ahn J , Ahn J , Kim J , Nam B , Ro J
Published: December 2010

Abstract #5105

Background: Preoperative paclitaxel (P) and gemcitabine (G) combination therapy given on D1/D8 every 3 weeks (wks) for 4 cycles was well tolerated and effective in stage II/III breast cancer (BC) in our previous phase II study, with an 18% pathological complete response (pCR) rate. Adding trastuzumab (H) to the preoperative chemotherapy increases both of the clinical and pathological response rates in HER2 positive BC patients (pts). Thus far, the highest pCR rate reported in the literature was obtained with anthracycline-based regimens in combination with trastuzumab. This study evaluated whether non-anthracycline combination chemotherapy with PGH could improve the pCR rate in HER2 positive BC. Methods: HER2 positive, stage II/III BC pts with cytologically confirmed axillary lymph node (LN), ≥ 18 years of age, with adequate organ function, and good performance status were eligible. No prior therapy was allowed. Pts received H intravenously (iv) at 4 mg/kg on D1 of the first cycle with subsequent weekly doses of 2 mg/kg in combination with P 80 mg/m2 and G 1,200 mg/m2, iv, on D1/D8 every 3 wks for 6 cycles. Within 2 wks postoperatively, patients received H 6 mg/kg every 3 wks for 11 cycles with tamoxifen or an aromatase inhibitor for 5 years if indicated. All pts received postoperative radiation therapy. Initial evaluation included sonogram and MRI of the breast, MUGA scan, or echocardiogram, and PET-CT. Results: All 53 planned pts were enrolled between April 2007 and February 2008. The median age was 43 years (range, 26–61 years), the median primary tumor size by sonogram was 5.3 cm (range, 2.0 to > 12 cm) with 89 % ≥ stage IIIA, 42% T3/T4, and 28% N3. Twenty four tumors (45%) were multiple and 20 tumors (38%) were ER positive. By May 2008, 47 patients completed surgery with a 74% breast conservation rate. Twenty-eight of 47 (60%; 95% CI, 45-72) patients achieved pCR in both the tumor and lymph node, with 68% (32/47; 95% CI, 54-80) pCR in the primary tumor, and 77% (36/47; 95% CI, 63-86) pCR in the axillary LN. Median metastatic focus in 21 positive LNs (n=11 pts) was 1 mm (range, <1–13mm). Grade III/IV adverse events (AE) were neutropenia (53%), febrile neutropenia (4%), and transient elevation of AST/ALT (9%). After 6 cycles of PGH chemotherapy, all patients maintained above normal LVEF. Conclusions: A remarkably high pCR was obtained by non-anthracyline based PGH combination therapy for HER2 positive stage II/III breast cancer. This combination is well tolerated with mild degree of AEs.  Supported by NCC Grant No 0610240-3. Trastuzumab, paclitaxel, and gemcitabine were supplied by Roche, CJ Cheiljedang CO., and Eli Lilly and CO., respectively.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5105.
Complete pathological response according to hormonal status, c-erbB2 and P53 in two neoadjuvant treatments in locally advanced breast cancers.
Authors: Giacchetti S , Lehmann-Che J , De Roquancourt A , Cuvier C , Turpin E , Marty M , Bertheau P , de Thé H , Espie M
Published: December 2010

Abstract #5107

Background: We previously showed that the p53 mutation is the major factor for response to dose-dense epirubicin-cyclophosphamide regimen (PLoS Med. 2007; Lancet 2002). Some years ago Taxanes became a standart treatment in neoadjuvant setting. We study two regimens of neoadjuvant anthracycline-based chemotherapy combined with high dose cyclophosphamide (C), or with Taxotere in locally advanced breast cancers (LABC) with respect to pathologic complete response (pCR).  Materials and methods: Between 1990 and 2003, 219 patients (pts) with LABC and/or inflammatory breast cancers (IBC) from one institution received 6 cycles (c) of dose dense C (1.2g/m2 d1)-epirubicin (E) (75mg/m2d1) q2w (SIM regimen). From 2003 to 2008, 132 pts with LABC and/or IBC from the same institution received 4 c of E (75mg/m2 d1) C(750mg/m2 d1) q3w followed by 4c of docetaxel 100mg/m2 d1q3w (ECT regimen). Surgery was done after chemotherapy and pCR was defined as no residual invasive tumour in breast and lymph nodes.  Results: 139/219 SIM pts (63.4 %) and 96/132 ECT (72.7 %) pts had frozen biopsies, surgery after chemotherapy, ER, c-erbB2 determination (IHC and /or RT-PCR) and p53 done by yeast functional complementation assay (FASAY) and were thus included in our study.        Conclusion:The high performance of the FASAY assay allows the demonstration of p53 role in the prediction of histological response in the ECT, as previously for the SIM regimen. In p53 mutant tumors, especially in ER- and ER- c-erbB2 negative tumors, high dose cyclophosphamide combined with E seems significantly better than Taxane regimen and needs to be studied prospectively. Future trials should determine the best regimen for p53 WT tumors.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5107.
Preliminary progression free survival and SPARC tumor correlatives from a phase II neoadjuvant trial of gemcitabine, epirubicin, and nab paclitaxel.
Authors: Yardley DA , Inhorn R , Daniel B , Daniel D , Naot Y , Zubkus J , Hanson S , Trieu V , Knauer D , Desai N , Burris HA
Published: December 2010

Abstract #5116

Background: Neoadjuvant combinations of gemcitabine (G), anthracyclines and taxanes have demonstrated significant activity with pCR rates of 20-25% albeit with significant myelosuppression. Secreted protein acidic rich in cysteine (SPARC) is an albumin binding protein that mediates intratumoral accumulation of nab-paclitaxel (nab-P) via a SPARC-albumin specific binding activity. This study was designed to evaluate a biweekly schedule of neoadjuvant nab paclitaxel (nab-P) with gemcitabine and epirubicin (E). SPARC tumor assessments were performed in consenting patients (pts) with subsequent pathologic and survival correlatives.  Methods: Eligibility: Clinical T1c-T4d and/or N0-3, M0 breast cancer (T1N0M0 excluded), ECOG PS 0-2, normal LVEF. ER/PR/HER2 obtained for all pts. Treatment: 6 cycles neoadjuvant G 2000 mg/m2, E 50 mg/m2, and nab-P 175 mg/m2 q14 days followed by surgery. Post operative therapy: 4 cycles G 2000 mg/m2 and nab-P 220 mg/m2 q14 days. Myeloid growth factors were mandated with all cycles. 2 antibody reagents were used to probe for SPARC expressions. For this study, level 3 immunohistochemical (IHC) SPARC staining was considered positive. Results: 123 pts have enrolled with pathologic responses available for 106. 82 pts consented to SPARC testing. Median age 51 (29-72). Median tumor size 4.5 cm. Histology: 81% ductal, 10% lobular, 9% other. 42% ER and PR negative. 55% clinical T3/T4 and 66% lymph node positive at presentation. G3/4 toxicity present in >5% of pts: neutropenia 16% (febrile neutropenia 1 pt), thrombocytopenia 9% with arthralgias 11%, fatigue 10%, and infection 7%. 20 pts did not complete study treatment for the following reasons: disease progression 7, toxicity 3, pt/MD request 5, and other 5. pCR was noted in 23 pts (22%) with PRs in 76 pts (71%), and 6 SD. SPARC IHC staining was available for 76 tumors. SPARC level 3 IHC staining was noted in 65 tumors (86%); 65% were associated with a PR or pCR. Median PFS was 23 months and overall survival at 24 months is 77%. Pts who relapsed ≤16 months from diagnosis were more likely to be triple negative (p = 0.04), or ER negative (p = 0.001), or PR negative (p = 0.0006). Conclusions: Neoadjuvant dose dense GEA is active and better tolerated than other gemcitabine/anthracycline/taxane combinations. The pCR rate of 22% compares favorably with other comparable neoadjuvant regimens albeit with minimal toxicity. Pts with early relapse defined as ≤16 months from diagnosis were more likely to demonstrate a triple negative phenotype or demonstrate estrogen or progesterone receptor negativity. SPARC tumor correlatives with progression free and overall survival are on ongoing and will be presented.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5116.
Phase II study of a 3-weekly liposome-encapsulated doxorubicin/docetaxel/pegfligrastrim in combination with weekly trastuzumab as primary treatment in HER2 positive early stage breast cancer patients (II-IIIa). GEICAM 2003-03 study.
Authors: Anton A , Ruiz-Simon A , Plazaola A , Calvo L , Segui M , Santaballa A , Muñoz M , Sanchez P , De Miguel A , Cirauqui B , Arcusa A , Oltra A , Puertolas T , Guerrero A
Published: December 2010

Abstract #5117

Objective: To assess the safety and efficacy of Myocet (M), Docetaxel (T), Trastuzumab (H) with prophylactic Pegfilgrastrim (N) as neoadjuvant chemotherapy in operable breast cancer patients (pts). The primary efficacy end point was pathologic complete response in the breast. Methods: Eligible pts had pathologically confirmed stage II or IIIA untreated breast cancer and HER2 overexpression determined by FISH in a central laboratory. M 50 mg/m2 and T 60 mg/m2 were given on day 1 and N on day 2 every 3 weeks for 6 cycles (Cy); H (4mg/Kgr loading dose, then 2 mg/Kgr/week) was given intravenously for 17 weeks, recommended dose in a phase I study (Proc ASCO 2007,25:596s Abstr.# 11.032). After all chemotherapy was completed, clinical responses were assessed. After surgery, pathological responses were evaluated using the Miller Payne scoring scale (MPSS). Results: 59 pts have been evaluated. Median age was 47.6 years (range 24-71) and median clinical tumour size 47.5 mm (range, 10-80). 19 pts (32.2%) presented with stage IIIA disease and 40 pts (67.8%) with stage II, 36 pts (61.0%) were premenopausal; 50 pts (84.8%) had histological grade 2-3 tumours; and 29 (49.2%) were ER-PgR-negative. All the pts received M and T 6 Cy with medium relative doses intense of 98.9% and 99.1% respectively. Objective clinical response rate was 84.7% (CI: 75.5-93.9) with 31 (52.5%) complete responses and 19 (32.2%) partial responses. 42 pts (71.2%) underwent conservative surgery, 17 pts (28.8%) achieved a pathological complete response in breast (Grade 5 in MPSS), of these, 16 pts (27.1%) achieved a pathological complete response in breast and axilar (Grade 5A+Grade 5D). Main grades (G) toxicities during MTHN treatment: leucopenia G3/4 was present in 18 pts (30.5%); neutropenia G3/4 in 17 pts (28.8%); febrile neutropenia G3 in 3 pts (5.1%); diarrhea G3 was present in 3 pts (5.1%); G2 rash in 2 pts (3.4%); G3 asthenia in 5 pts (8.5%) and stomatitis G3 in 1 pt (1.7%). 8 pts (13.6%) experienced asymptomatic and reversible cardiac left ventricular function G2. Conclusions: Concomitant administration of M plus THN is highly effective and active regimen with little toxicity in pts with HER2+ and early stage breast cancer.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5117.
Phase II trial of neoadjuvant chemotherapy of sequential FEC100 followed by docetaxel, carboplatin and trastuzumab (TCH) for HER-2 over-expressing locally advanced breast cancer (LABC): a multi-centre study from British Columbia.
Authors: Chia S , Bryce C , Pansegrau G , Macpherson N , Ellard S , Jepson D , Yu C , Nuraney S , Attwell A , Hayes M , Kennecke H , Gelmon K
Published: December 2010

Abstract #5118

Background: The role of trastuzumab either concurrent or sequential with adjuvant chemotherapy have clearly demonstrated significant benefits in early stage HER-2 positive breast cancer. There is now an accumulation of phase II and III trials also demonstrating improved pathological complete responses (pCR) in HER-2 positive breast cancer with neoadjuvant trastuzumab concurrent with chemotherapy. The number of patients on these trials are significantly fewer, and many of these trials are a mixture of primary operable and LABC. We have completed a multi-centre phase II trial of neoadjuvant chemotherapy and trastuzumab in HER-2 positive LABC.  Methods: Women with HER-2 positive (IHC 3+ or FISH+) stage IIB-IIIC breast cancer were enrolled. Treatment consisted of 4 cycles of FEC100 (5-FU 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2) followed by 4 cycles of TCH (Docetaxel 75 mg/m2, carboplatin AUC 6, trastuzumab 8 mg/kg loading then 6 mg/kg q3 weekly). Trastuzumab was also continued adjuvantly for 9 months following chemotherapy and surgery. Cardiac monitoring every 3 months was mandated. A correlative translational component with baseline and interval biopsies and serum collection was also performed.  Results: A total of 30 patients (3 stage IIB; 14 IIIA; 10 IIIB and 3 IIIC) over a 3 year time period in 4 centres were accrued. Median age was 49 years (26-77 years). 60% of tumours were ER negative. There was one clinical CHF and 2 asymptomatic falls in LVEF requiring early discontinuation of trastuzumab. There were 3 episodes (10%) of febrile neutropenia. Seven patients underwent adjuvant radiotherapy prior to surgery. The pCR rate (breast and axilla) for the entire study population was 60% (18/30). There have been 3 recurrences so far (all biopsy proven) – of which 2 were brain metastases only. Further details on toxicity and changes in LVEF will be presented.  Conclusions: This multi-centre phase II trial clearly demonstrates significant activity (pCR 60%) for neoadjuvant anthracyclines followed by concurrent taxane, platinum and trastuzumab in a HER-2 positive LABC population. Overall the treatment regimen was well tolerated. Brain metastases however appear to be a common site of relapse in this high risk patient population and further treatment strategies directed at this site should be investigated.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5118.
Accuracy of DCE – MRI in predicting response in patients treated with taxane based neoadjuvant chemotherapy.
Authors: Garimella V , Elfadl D , Elahi MB , Mahapatra TK , McManus PL , Chaturvedi A , Upadhyay S , O'Neil P , Turnbull LW , Drew PJ
Published: December 2010

Abstract #5120

Background: Neoadjuvant chemotherapy for locally advanced breast cancer is an established treatment option. Several studies have shown DCE-MRI scanning to be the most accurate investigation to assess response to EC chemotherapy. Recent trials have shown that addition of Taxanes increases the overall response rate and the rate of breast conserving surgery. Taxanes act by inhibiting angiogenesis in the tumour and this could potentially affect the quality of the post treatment scan images as DCE-MR scan and cause inappropriate decisions regarding the required surgery.  Aim: To compare the accuracy of DCE-MR scan in identifying residual disease in patients treated with FEC (Fluoro uracil, Epirubicin, Cyclophosphamide) vs EC (Epirubicin, Cyclophosphamide) followed by Taxane.  Methods: Patients treated with primary chemotherapy who subsequently underwent breast conserving surgery were identified from a prospectively maintained database. Clinical details including chemotherapy regimes, pre and post chemotherapy MRI data, number of surgical procedures and histological parameters of the excised specimen were obtained.  Results: A total of 121 patients treated with primary chemotherapy were identified. Of these, 76 were treated with FEC or EC based chemotherapy and 45 were treated with EC+Taxane. DCE-MRI was significantly less accurate (p<0.05) when predicting the size of residual disease in the Taxane group.    Conclusion: DCE MR scan is not as accurate for quantifying size of residual disease in patients treated with taxane when compared with patients treated with traditional FEC/EC based primary chemotherapy. This should be considered when planning surgery after neoadjuvant therapy.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5120.
The response to neoadjuvant chemotherapy and prognosis of triple-negative breast cancer patients.
Authors: Nakano E , Hojo T , Masumura K , Kikuyama M , Akashi S , Kinoshita T
Published: December 2010

Abstract #5121

Purpose: It is said that triple negative breast cancer (TNBC) has poor prognosis. However, many study shows TNBC has better response to chemotherapy. Since neoadjuvant chemotherapy plays an important role to TNBC, we compared clinical and pathological response rate and prognosis between TNBC and non-TNBC.  Patients and methods: This analysis retrospectively collected 2563 breast cancer patients for StageI-III who underwent surgery between January 2000 and September 2004 (median: 3.9 years) at National Cancer Center, Tokyo, Japan. We defined TNBC as Estorpgen and progesterone receptor negative and HER2 score 0-2+ by immnohistological report. There were 91 TNBC patients (23.1%) out of 400 patients (15.6%) who underwent neoadjuvant chemotherapy. Clinical and pathological response rate and Four-year progression free survival were compared between TNBC and non-TNBC.  Results: There were 91 TNBC patients (23.1%). TNBC patients compared with non-TNBC had tendency to achieve cCR (91% vs 78%; p=.058) although TNBC had higher rate for cPD (6.6% vs 1.7%; p <.0001). Also TNBC tended to have higher pathological CR rate of which we classified pCR only for grade 3 cases, compared to non-TNBC (13.1% vs 7.2%; p= .042 ). Interestingly HER2 overexpression type also had higher rate for pCR. As for pPD rate, TNBC had similar rate compared to non-TNBC (5.5% v 4.3%). Four-year progression free- survival rate was higher for non-TNBC. However, TNBC had higher Four-year survival free rate only when pCR were achieved after neoadjuvant chemotherapy (99% vs 82%; p=.02).  Conclusion: Patients with TNBC tend to have clinical and pathological response of either CR or PD. Although non-TNBC had better prognosis by four-year survival free rate, TNBC could have better prognosis if neoadjuvant chemotherapy resulted in pCR. There may be some way to predict the efficacy of neoadjuvant chemotherapy and prognosis by analyzing the shrink pattern.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5121.
A randomized phase II trial of preoperative docetaxel (D) and capecitabine (C) given sequentially or concurrently for Her2 negative breast cancers.
Authors: Harichand-Herdt S , Zelnak A , Styblo T , Rizzo M , Gabram S , Bumpers H , D'Orsi C , Carlson K , Senior-Crosby D , Sellers N , Pierce T , Hicklin D , Srinivasiah J , Schnell F , Hermann R , O'Regan R
Published: December 2010

Abstract #5122

Background The efficacy of D and C as single agents and in combination is well established in the treatment of metastatic breast cancer. Novel sequential and concurrent regimens of D and C were evaluated in patients with her2-negative breast cancer eligible for preoperative therapy. MethodsPatients with Stage I (>1.0cm), II or III, Her2- breast cancer were randomized to two treatment arms: Arm A: sequential therapy with D 100 mg/m2 Q 3 weeks for 4 cycles, followed by C 1000mg/m2 BID on days 1-14 of a 3-week cycle, for 4 cycles; Arm B: concurrent therapy with D 50mg/m2 on day 1 and C 1000mg/m2 BID on days 1-7 of a 2-week cycle for 8 cycles. The planned total dose of D and C and number of cycles were identical on both arms. Tissue was collected at baseline, midway and post-therapy for correlative studies. Endpoints included pathologic complete response (pCR) rate, response rate, and toxicity. Results To date 38 of 80 planned patients have been accrued (4/07-6/08). Data are available for 33 patients; 16 African American (AA) (49%), 16 Caucasian (49%), and 1 Hispanic (2%). Patients were accrued from a university center (59%), county hospital (31%) and community sites (10%). Histology: Infiltrating ductal carcinoma (76%), infiltrating lobular carcinoma (15%), metaplastic tumors (6%), mucinous carcinoma (3%). Four patients had inflammatory breast cancer. 17 patients (52%) had ER+ or PR+ tumors and 16 (48%) had ER-/PR- tumors (triple negative tumors or TNT). The average tumor size at baseline was 4.0cm+/-3.0cm. In 29 patients who completed therapy, both regimens were relatively well tolerated: 9 patients (Arm A, N=3 (23%); Arm B, N=6 (38%)) had grade 3 toxicity, predominantly hand-foot syndrome, diarrhea or neuropathy. Dose reductions were required for 12 patients due to toxicity (11 required for C, 1 for D). To date, the pCR rate is 7%, observed only in AA patients with TNTs. In this subgroup the pCR rate was 18%.    Discussion This study represents the first effort to accrue patients through a Georgia-based trial network, providing a unique opportunity to treat patients from a region with a large AA population. Our preliminary results suggest modest activity of D and C, with greater activity in the concurrent arm and in AA patients with TNTs. An official interim analysis is planned and updated results will be presented. Correlative studies which focus on molecular differences in responders and non-responders, particularly in the TNT group will be presented.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5122.
Dosimetric analysis of prone versus supine concomitant boost IMRT technique for whole breast radiotherapy: prone is better in reducing cardiac dose for left sided breast cancer.
Authors: Reyes V , Lymberis SC , Becker S , Racsa M , Jozsef G , DeWyngaert K , Formenti SC
Published: December 2010

Abstract #5129

Introduction: Prone whole breast radiotherapy is feasible and can be delivered with a hypofractionated, concomitant boost IMRT regimen (JCO, vol. 25, 16, 2007). We hypothesized that in occasional patients a supine set-up could better spare heart and lung while optimally treating the target breast. We designed NYU 05-181 protocol to test this hypothesis. Herein we performed a dosimetric analysis by comparing treatment plans in both the prone and supine position for patients with left breast cancer.  Methods: Early stage breast cancer patients after segmental mastectomy are eligible for this IRB-approved prospective study. A supine CT simulation with images acquired every 2.5 mm is performed. The patient is then repositioned prone using a dedicated breast mattress and a second CT is obtained. The treatment volume (TV) is the whole index breast, determined according to conventional breast simulation with the patient in the supine position. Each patient is planned in both positions and is treated based on the optimal plan defined as the one that best satisfies each of the following criteria: 1) inclusion of the TV; 2) maximum heart sparing; 3) maximum lung sparing. Dosimetric analysis of the prone and supine treatment plans was performed to compare coverage of the whole breast, PTV coverage of the tumor bed, and the dose to lung and heart.  Results: Twenty-five patients with a left breast cancer were analyzed. Five patients were treated supine, and 20 patients were treated prone because this position enabled optimal breast coverage and heart and lung sparing. However, all patients were simulated and planned in both positions. As shown in Table 1, whole breast coverage is better for the prone position although not statistically significant (p=0.38), PTV coverage was superior in the prone position (p<0.001).    Importantly, heart dose was not increased in the prone position (p<0.001). Additionally, lung dose was markedly reduced in the prone position (p<0.001).  Conclusions: Contrary to many concerns that the prone position leads to anterior displacement of the heart within the treatment field this was only observed in 5 of the 25 patients. This dosimetric analysis demonstrates that in fact prone breast irradiation when compared to supine results in reduced exposure to both heart and lung while enabling complete coverage of the whole breast and tumor bed for the vast majority of patients. There are few left breast patients who are better positioned supine and the NYU protocol 05-181 is currently accruing to fully characterize this infrequent subset.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5129.
Phase I/II study evaluating early tolerance in breast cancer patients undergoing accelerated partial breast irradiation treated with MammoSite balloon breast brachytherapy catheter using a two-day dose schedule.
Authors: Wallace MF , Martinez AA , Chen PY , Ghilezan MI , Benitez PR , Brown E , Vicini FA
Published: December 2010

Abstract #5131

Purpose: Initial phase I/II results utilizing balloon brachytherapy to deliver accelerated partial breast irradiation (APBI) in only 2-days in patients with early stage breast cancer are presented.  Materials and Methods: From 3/2004 – 8/2007, 45 patients received adjuvant radiation therapy after lumpectomy with balloon brachytherapy in a phase I/II trial delivering 2800 cGy in 4 fractions of 700 cGy to a depth of 1 cm from the applicator surface. Inclusion criteria for the protocol included: (1) patient age > 40 years, (2) pathological confirmation of stage 0/I/II breast carcinoma, (3) > 3 cm tumor size, (4) < 3 pathologically positive lymph nodes, and (5) negative margins (per NSABP criteria). Toxicities were evaluated using the NCI CTAE v3.0 scale and cosmesis (Harvard Criteria) was documented at > 6 months.  Results: The median age was 66 years (48-83) and median skin spacing was 12 mm (8-24). The median follow-up was 11.4 months (5.4-48 mo) with 20 patients (44%) followed greater than one year, 11 (24%) greater than 2 years and 6 (13%) greater than 3 years. At < 6 mo (n=45), grade II toxicity rates were 9% radiation dermatitis (n=4), 13% breast pain (n=6), 2% edema (n=1), and 2% hyperpigmentation (n=1). Grade III breast pain was reported in 13% (n=6). At > 6 months (n=43), grade II radiation dermatitis, induration, and hypopigmentation were 2% (n=1), grade III breast pain was reported in 2% (n=1). Infection was 16% (n=7) at < 6 mo and 2% (n=1) at > 6 mo. Of these pts, only 4% (n=2) had a positive culture, whereas the others were treated empirically due to brisk erythema. Persistent seroma > 6 months was 30% (n=13). FN was seen in 9% (n=4), but only 1 pt required treatment. Rib fracture was seen in 5% (n=2). Cosmesis was good/excellent in 96% and fair in 4%.  Conclusions: Treatment with balloon brachytherapy using a 2-day dose schedule resulted acceptable rates of grade II/III chronic toxicity rates and similar cosmetic results observed with standard 5-day APBI schedule.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5131.
Preliminary result of a mono-institutional, prospective study of skin and cardiac toxicities in breast cancer patients treated by concurrent adjuvant trastuzumab and radiotherapy involving in most cases the internal mammary chain.
Authors: Bollet MA , Kirova YM , Granger B , Caussa L , Savignoni A , Pierga J , Campana F , Dendale R , Fourquet A
Published: December 2010

Abstract #5132

Purpose: This study aimed to evaluate the skin and heart toxicities of a concurrent adjuvant trastuzumab (T) and radiotherapy (RT) for breast cancer (BC), especially in the case of IMC irradiation.  Patients and methods: Prospective study of 57 pts treated at the Institut Curie between 02/2004 and 01/2007 by concurrent T-RT for non-metastatic BC. The perfusion of trastuzumab started either with or after chemotherapy (CT). RT, started at least 4 weeks after the completion of anthracycline-based chemotherapy, consisted of either whole breast (+/- boost) or chest wall normo-fractionated irradiation. When indicated the internal mammary chain (IMC) and supra/infra-clavicular lymph nodes were also irradiated. Left ventricular ejection fractions (LEVF), assessed at baseline, before start of RT (pre-RT), after completion of RT and then every 4-6 months with either echocardiography or multiple gated acquisition scanning, were considered normal if ≥50% or stated so by the cardiologist. A normal LVEF at baseline was one of the inclusion criteria. Skin toxicity was evaluated using CTCAEV3.  Results: Median age was 49 years (25-80). CT with anthracycline was administered in 84% (48 pts) with either doxorubicine for 6 pts (median total dose 300 mg/m²) or epirubicine for 42 pts (median total dose 300mg/m²). All but one patient (treated weekly) received T every three weeks (8mg/kg followed by 6mg/kg) for a median duration of 12 months (6-33). The treated breast was the left one in 46% (26 pts). The IMC was irradiated in 88% (50 pts). Median follow-up for LVEF assessment was 13 months (2-33). LVEF at pre-RT were normal in 55 pts (100%, 2 Missing Data), at post-RT in 56 pts (98%, no MD) and at last follow-up in 54 pts (95%, no MD).  Overall, there were 2 grade 0, 44 grade I, 11 grade II skin reactions. For the 27 patients with a skin toxicity assessment after 6months, late skin toxicity was grade 0 in 22 pts, grade 1 in 4, grade 2 in 1. There was no skin toxicity graded higher than 2.  Conclusion: In this preliminary study of BC patients treated with T-RT with, in most cases, anthracycline-based CT and IMC irradiation, there was no significant increase in the rate of abnormal LVEF after concurrent T-RT and the skin toxicity was acceptable in routine. More patients and a longer follow-up are needed to ascertain that this regimen remains safe.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5132.