bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P1-12-01: Preoperative Endocrine Therapy with Tamoxifen and Goserelin Acetate for Hormone Receptor-Positive Premenopausal Patients
Authors: Shimizu D , Ishikawa T , Yamada A , Tanaabe M , Chishima T , Sasaki T , Endo I. 
Published: April 2011

Abstract
Background: Clinical trials have consistently shown that the response rates of hormone receptor-positive breast cancer patients to neoadjuvant chemotherapy are low. Preoperative endocrine therapy has therefore become a logical alternative for such patients. Several researchers have reported favorable response rates in postmenopausal women. However, the effectiveness of preoperative endocrine therapy for premenopausal women remains unknown. The aim of this study was to evaluate the potential benefits of preoperative endocrine therapy for premenopausal women.
Materials and methods: Forty premenopausal patients with operable estrogen receptor (ER)-positive breast cancer were consecutively treated with neoadjuvant therapy with tamoxifen and Goserelin acetate for 3 months. The patients eligible for this study included clinically node-negative patients with tumors that were less than 2 cm in diameter and negative for human epidermal growth factor receptor 2 (HER2). All the patients were clinically evaluated using ultrasonograpy before and after the endocrine therapy. Further, core-needle biopsy specimens obtained before administration of the endocrine therapy and surgical specimens were pathologically evaluated for ER, progesterone receptor (PgR), HER2, p53, and Ki67 expressions. This study was approved by our institutional IRB.
Results: The patients included in this study were 30-52 years old (median age, 43 years). The size of the tumor was 0.9-2.0 cm (median, 1.5 cm).
The clinical response rate was 20% (8/40) and disease progression was not observed. In the case of 39 of the 40 patients, grade 0 or grade 1 pathological response was observed. Clinical responses were not correlated with pathological responses. The ER expression level before the endocrine therapy differed from that after the therapy in the case of 8% (2/40) of the patients (increased in 4% and decreased in 4%). Further, PgR expression was altered in the case of 50% (20/40) of the patients (increased in 8% and decreased in 42%). Moreover, Ki67 expression was decreased in 90% (36/40) of the patients after the endocrine therapy.
Conclusions: This is the first report on neoadjuvant endocrine therapy for premenopausal patients. Disease progression 3 months after the endocrine therapy was not observed. Because the expressions of Ki67 and PgR decreased, these molecules might be candidate markers of endocrine responsiveness in premenopausal patients. To confirm this assumption, further evaluations involving tumors of a larger size, longer observational period, and more number of eligible patients are planned to be conducted.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-12-01.
Abstract P1-12-04: Long Term Follow-Up of a Pilot Trial of Pre-Operative (Neoadjuvant) Letrozole in Combination with Bevacizumab in Post-Menopausal Women with Newly Diagnosed Estrogen and/or Progesterone Receptor Positive Breast Cancer
Authors: Forero A , Saleh M , Galleshaw J , Jones C , Nabell L , Carpenter J , Falkson C , Krontiras H , Urist M , Bland K , De Los Santos J , Meredith R , Caterinicchia V , Bernreuter W , O'Malley J , Yufeng L , LoBuglio A. 
Published: April 2011

Abstract
Introduction: Overexpression of vascular endothelial growth factor (VEGF) in breast cancer tumors has been associated with resistance to anti-estrogen adjuvant therapy. We designed a pilot study of neoadjuvant letrozole and bevacizumab (anti-VEGF) to assess feasibility and short term efficacy in post-menopausal women with stage II/III, ER/PR positive breast cancer. Patients and Methods: Patients were treated with a neoadjuvant regimen of letrozole, 2.5 mg/day (PO) and bevacizumab 15 mg/kg every 3 weeks (IV) for a total of 24 weeks prior to surgical treatment of their breast cancer. Patients were followed for toxicity at three week intervals and tumor assessment (physical exam and tumor ultrasound) at six week intervals. Results: Twenty-five evaluable patients were treated. The regimen was well tolerated except for two patients who were taken off-study for difficult to control hypertension. Objective clinical response occurred in 17/25 patients (68%) including 16% CR and 52% PR. The four patients with clinical CR had pathologic CR in their breasts (16%) although one had residual tumor cells in axillary nodes. Two of the 17 responding patients were lost to follow-up; with a median follow-up of 50 months, no relapses have been seen in the 15 responsive patients, including 10 patients who received no adjuvant chemotherapy. Two patients with progressive disease at 9 and 16 weeks received neoadjuvant chemotherapy, surgery and radiation. One of these patients relapsed at 35 months and the other is NED at 44 months. Four patients had stable disease and all received adjuvant chemotherapy; one patient relapsed at 25 months, and the reminder are NED at 44-52 months. Overall, 2 out of 21 patients with adequate follow-up had disease reoccurrence (9.5%) at a median follow-up of 45 months. Conclusion: Combination neoadjuvant therapy with letrozole and bevacizumab was well tolerated and resulted in impressive clinical and pathologic responses. Data suggest that patients having an objective response to neoadjuvant therapy had excellent 4 year disease-free survival (100%) while relapsed occurred in 2 out of 6 patients who failed to have an objective response despite additional neoadjuvant or adjuvant chemotherapy. The Breast Cancer Translational Research Consortium has an ongoing randomized phase II trial of letrozole ± bevacizumab in this patient population.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-12-04.
Abstract P1-12-06: Outcome of Frail Elderly Patients Treated with Letrozole Alone
Authors: Dixon JMJ , Renshaw L , Keys J , Leeper AD , Williams L , Evans DB. 
Published: April 2011

Abstract
Background
There are no data on the rate of progression of infirm or elderly postmenopausal patients unfit for surgery who have been treated with aromatase inhibiors alone. The aim was to determine the rate of disease control in a series of patients treated in the Edinburgh Breast Unit. Patients
79 patients with a median age of 81 years (range 57 to 98) with ER rich breast cancers (Allred score 6-8) have been treated with letrozole alone. The median follow up is 2.06 years, range 0.34 to 7.64. Of 71 patients with HER2 results, 59 (83%) were negative and 12 (17%) were positive.
Results
At two years, 65% were progression-free. By five years, this was 43%. The median time to first progression was 3.1 years (95% CI 1.7 to 4.5). By the Log Rank test, there was evidence of a significant difference between HER2+ve and-ve cancers (p=0.014). Median time to first progression for HER2-ve patients was 3.1 years (95% CI 1.9 to 4.2) and for HER2+ve patients was 1.8 years (95% CI 0.7 to 2.8). By two years, 67% of HER2-ve patients were progression-free, while 34% of the HER2+ve patients remained progression-free. At five years, 32% of the HER2-ve patients were progression free, however HER2+ve patients had insufficient follow up to estimate the 5 year progression-free rate. At two years, 77% of patients were still alive. By five years, that number was 33%. The median survival time was only 3.2 years (95% CI 2.4 to 4.1).
There was no evidence to suggest a difference in mortality rates between HER2+ve and HER2-ve patients (p=0.79). Median survival time for HER2- ve patients was 2.6 years (95% CI 1.6 to 3.7) and for HER2+ve patients it was 3.0 years (95% CI 2.5 to 3.5). Conclusions
In an elderly unfit population with ER rich breast cancer two thirds of these women will have their cancer controlled at 2 years by letrozole alone. HER2+ve cancers have a significantly shorter progression free survival than HER2-ve cancers.
For older or infirm women unfit for surgegy with ER rich breast cancers, letrozole will control their cancer in the majority to the time of their death which was from other causes in all patients in this series.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-12-06.
Abstract P1-13-03: Is Bone Biopsy of Metastatic Sites Useful in Advanced Breast Cancer Management?
Authors: Aurilio G , Sciandivasci A , Bagnardi V , Della Vigna P , Monfardini L , Preda L , Rizzo S , Padrenostro M , Renne G , Munzone E , Cullurà D , Petrella MC , Bellomi M , Nolè F. 
Published: April 2011

Abstract
Background: Biopsies of metastatic sites are not recommended in clinical practice to evaluate changes in biological features in advanced breast cancer (ABC) women. We assessed discordance in expression levels for estrogen receptor (ER), progesterone receptor (PgR) and epidermal growth factor receptor 2 (HER2), between primary tumor and bone metastases and its clinical impact on patient management.
Material and Methods: We retrospectively analyzed 109 ABC patients (pts) underwent computed tomography guided bone biopsy at the European Institute of Oncology in Milan, Italy, from 1997 to 2009. Data on ER and PgR status [positive if ≥1% by immunohistochemistry (IHC)] and on HER2 status (positive if IHC3+ and/or FISH amplified), both primary tumor and bone metastases were collected. Fisher and McNemar's test were used for statistical analysis.
Results: Median time from primary diagnosis to bone biopsy was 4.2 years (range 0-18.9). Overall discordance rate (ODR) in ER expression was 20.5% (95% CI: 13.4%-29.5%): 3/7 pts (42.9%) shifted from ER negative to positive and 19/100 pts (19%) from ER positive to negative [p=0.0006]. ODR in PgR expression was 43.9% (95% CI: 34.3%-53.8%): 4/21 pts (19%) changed from PgR negative to positive and 43/86 pts (50%) from PgR positive to negative [P&lt;0.0001]. ODR in HER2 status was 6.9% (95% CI: 2.6%-14.6%): 4/78 pts (5.1%) changed from HER2 negative to positive and 2/8 pts (25%) turned from HER2 positive to negative [p=0.41]. Thirteen out of 21 pts (61.9%) with discordant ER status and 23/77 pts (29.8%) with concordant ER status [p=0.01] changed endocrine therapy; there were no differences in chemotherapy [p=0.80]. Four out of 6 pts (66.6%) with discordant HER2 status and 6/72 pts (8.3%) with concordant HER2 status changed immunologic therapy [p=0.002], 3/6 pts (50%) started trastuzumab and 1/6 patient (16.6%) stopped it; there were no differences in chemotherapy [p=0.68]. All pts well tolerated the invasive procedure, requiring only local analgesia. Discussion: Our analysis showed that receptor profile may significantly change between primary breast cancer and bone metastases, with relevant impact on therapy. Bone biopsy might be useful and should be considered in selected cases to optimize therapeutic choices. Large prospective trials are needed to investigate these outcomes.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-13-03.
Abstract P1-13-05: The Effect of Treatment with Denosumab or Zoledronic Acid on Health-Related Quality of Life in Patients with Metastatic Breast Cancer
Authors: Fallowfield L , Patrick D , Body J-J , Lipton A , Tonkin KS , Qian Y , Zhao Y , Jiang Q , Braun A , Dansey R , Chung K. 
Published: April 2011

Abstract
Background: Patients with breast cancer and bone metastases often experience skeletal-related events (SREs) and pain, which may impact health-related quality of life (HRQoL). Denosumab is a fully human monoclonal antibody against RANKL shown to be superior in delaying/preventing SREs and more effective in delaying moderate or severe pain in patients with advanced breast cancer compared with zoledronic acid (ZA). Previously reported results from this study population showed that both denosumab and ZA patients showed improvement or maintenance in HRQoL relative to baseline (BL), and a greater proportion of denosumab-treated patients had a clinically meaningful improvement in HRQoL. We now describe the effect of denosumab and ZA treatment on HRQoL among patients with varying degrees of pain at BL.
Methods: Enrolled patients received subcutaneous (SC) denosumab 120 mg or intravenous (IV) ZA 4 mg every 4 weeks in a double-blind, double-dummy fashion. Pain was evaluated using the Brief Pain Inventory — Short Form (BPI). Patients were divided into 2 subgroups based on the level of pain reported at BL: no/mild pain or moderate/severe pain. Patients completed the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire at BL, day 8, and before each monthly visit to assess overall HRQoL. Higher scores (range 0 to 108) represent better HRQoL. Improvement, maintenance, and worsening of HRQoL were assessed through month 18, when 30% of patients had dropped out due to death, disease progression, or withdrawal of consent. A change of ≥5 points (increase or decrease) in the FACT-G total score was considered a meaningful improvement.
Results: Among patients who reported no/mild pain at baseline, more denosumab-treated patients had a ≥5-point increase in their FACT-G score from month 4 onwards. Over the 18 month period, an average of 4.1% more (range: −0.6% to 9.3%) denosumab-treated patients experienced meaningful improvement in HRQoL than ZA-treated patients. There were also fewer denosumab-treated patients experiencing ≥5-point decrease in HRQoL over 18 months (average of 2.4% fewer [range:-4.4% to 6.3% fewer]). Similar patterns were also noted for patients with moderate/severe pain at baseline. An average of 3.0% more (range:-1.7% to 7.9%) denosumab-treated patients had ≥5-point increase in FACT-G scores compared with ZA-treated patients over 18 months. A lower proportion of denosumab-treated patients (3.5% fewer [range: −1.1% to 11.5% fewer]) than ZA-treated patients had a decrease ≥5-points in their FACT-G score over 18 months.
Conclusion: In patients with breast cancer and bone metastases, a greater proportion treated with denosumab than ZA had a meaningful improvement in HRQoL regardless of their pain level at BL.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-13-05.
Abstract P1-14-04: Clinical Outcomes of Brain Metastasis by Lapatinib (L) and Capecitabine (C) in an Open-Label Expanded Access Study among Korean Patients with HER2 Positive Metastatic Breast Cancer
Authors: Ro J , Park S , Kim S-B , Kim T-Y , Im Y-H , Rha SY , Chung JS , Moon H , Santillana S. 
Published: April 2011

Abstract
Background: The L-Expanded Access Program (LEAP) was designed to provide access to L/C for HER2+ patients (pts) who previously received anthracycline, taxane, and trastuzumab. In earlier registration trial, CNS metastases occurred in fewer women receiving L/C therapy compared with C alone. Although L therapy has shown efficacy in brain metastasis (BM), it has not been well elucidated in relationship with the outcomes of systemic disease.
Patients and methods : Enrollment in LEAP lasted between Jan. 2007 and Apr. 2008 at 6 centers in Korea. Exploratory analysis on clinical outcomes of brain metastasis was performed.
Results: Total 187 pts enrolled in LEAP. The median treatment duration of all pts was 19.0 weeks (range, 1.4 — 146.9). The median progression free survival and overall survival (OS) of all pts were 20.0 (95% confidence interval [CI]= 18.6-24.0) and 60.0 (95% CI= 50.3-72.7) weeks, respectively. All patients received prior trastuzumab therapy, and 48.7% received prior capecitabine. Among 58 enrolled pts who had BM diagnosed before start L/C therapy, 55 pts were included for the analysis excluding 3 pts (1-consent withdrawal and 2-&lt;3 weeks trial). Fifteen pts had single BM. Majority were HER2 IHC 3+ or FISH +, and 48% were both ER/PR-. Prior to EAP enrollment, 35 pts underwent whole brain radiation, 10 pts SRS or gamma knife, 3 pts local excision, 1 pt had leptomeningeal disease only receiving intrathecal therapy, and 6 pts did not receive local CNS therapy. Four pts underwent more than one modality of local CNS therapy. Of 50 pts evaluable for response, 9.1%, achieved or remained CR; 45.5% had some degree of shrinkage of BM; 14.5%, no change (SD) ≥6mo; 7.3%, SD &lt;6mo; 14.5% developed PD or recurrence of BM. Median TTP of pts (n=53) with BM on L/C therapy was 30.7 weeks (95% CI=25.0-35.1) and median OS (n=55) was 53.1 weeks (95% CI= 42.3-78.0). From the multivariate analysis, TTP of BM was significantly associated with response of BM (HR, 20.3, 95% CI=7.3-56.0, P&lt;0.001). OS of pts with BM was significantly longer with tumors of ER or PR+ status (HR, 3.10, 95% CI=1.55-6.19, p=0.0014), and who responded in systemic disease and brain (HR, 4.5, 95% CI= 2.2-9.2, P&lt;0.0001). Of remaining 129 pts, 8 pts (6.2%) developed new BM on EAP.
Conclusion: Overall survival of patients with brain metastasis who received lapatinib plus capecitabine was prolonged specifically in responders of both brain and extracranial disease. Patients with hormone receptor positive tumors had longer survival compared with those of hormone receptor negative disease.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-14-04.
Abstract P1-15-02: Impact of Retinoblastoma (RB) Tumor Suppressor Pathway on Ductal Carcinoma In Situ (DCIS) Recurrence
Authors: Witkiewicz AK , Kline J , Freydin B , Apanasovich T , Schwartz G , Knudsen E. 
Published: April 2011

Abstract
The retinoblastoma (RB) tumor suppressor is functionally inactivated at high frequency in human malignancies including breast cancer. By immunohistochemistry loss of RB function is associated with p16ink4a overexpression and high Ki67 proliferation index.We have previously shown that loss of RB results in dramatic upregulation of genes associated with tumorigenesis and is a key determinant of therapeutic response in invasive breast carcinoma. Recently publish data indicate that RB pathway dysregulation plays an important role in DCIS progression to invasive carcinoma. The aim of this study was to evaluate the expression p16ink4a and Ki67 (indicative of RB loss) in a large cohort of DCIS patients treated at one institution with wide-excision and close follow-up. Material and Methods
149 DCIS patients were included in the study. Expression of p16ink4a and Ki67 was assessed by employing a standard immunoperoxidase method with ani-p16ink4a (MTM Laboratories Westborough, MA) and anti-Ki67 (AbCam Cambridge, MA) antibodies. The p16ink4a staining in DCIS epithelium was scored semi-quantitatively as negative (0; no staining), weak (1;staining in less than 25% of cells), moderate (2; defined as staining in 25-75% of cells) and strong (3; &gt;75% of cells staining). For statistical analysis, the original p16ink4a scores (0, 1, 2, 3) were dichotomized as low (0,1) vs. high (2-3) and original ki67 scores were dichotomized as low (&lt;= 10%) vs. high (&gt; 10%). Stromal p16 staining was scored as absent or present.
Association between p16ink4a and Ki67 and nuclear grade, necrosis, hormone receptor and Her2 expression as well as recurrence was assessed using Fisher's exact test. The Cox proportional hazard model was used for analyses of time to recurrence. Results
There was a statistically significant association between high p16ink4a and Ki67 expression in DCIS epithelium and triple negative as well as Her2 positive DCIS subtypes. Significant association was detected between high expression of p16 and Ki67 in DCIS epithelium and DCIS recurrence (p=0.005). Stromal expression of p16 was the strongest predictor of DCIS recurrence (p &lt; 0.0001). In multivariate Cox model DCIS cases with high expression of p16 and Ki67 in epithelium and stromal p16 expression had the shortest time to recurrence.
Conclusion
RB pathway dysregulation in DCIS epithelium as well as stromal expression of p16ink4a indicative of senescence are associated with DCIS recurrence.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-15-02.
Abstract P1-15-03: Eight-Year Update of a Prospective Study of Wide Excision Alone for Ductal Carcinoma In Situ (DCIS) of the Breast
Authors: Wong JS , Smith BL , Troyan SL , Gadd MA , Gelman R , Lester SC , Schnitt SJ , Sgroi DC , Chen Y-H , Silver BJ , Harris JR. 
Published: April 2011

Abstract
Background: The need for radiation therapy (RT) in conservatively managed DCIS is a source of ongoing debate. This is an updated analysis of a phase II prospective study of wide excision alone for DCIS. The study was activated in May 1995 and closed in July 2002 following accrual of 158 patients because the number of local recurrences (LR) met the predetermined stopping rules. The objective of the analysis is to update the distribution and cumulative incidence of events (LR, contralateral breast cancer [CBC], second malignancy and death from other causes). Materials and Methods: A total of 158 patients had DCIS with predominant nuclear grade 1 or 2, a mammographic extent of ≥2.5 cm, and excision with final microscopic margins of ≥1 cm or a re-excision without residual DCIS. Tamoxifen was not permitted. The results presented are from the 8-year analysis (8-year minimum potential follow-up time). Twenty-six patients without recurrence who were followed less than 8 years were excluded from the analysis as were 7 first events (4 LR) that occurred beyond 8 years of follow-up; the analysis thus includes 132 patients and 36 first events. Cumulative incidence curves were generated to assess the rates of LR or other events. Median follow up time was 10 years. Results: Overall, 36/132 patients (27%) had a first event as of April 2010. Of these 36 events, 19 were LR, 13 were CBC, 1 was a second malignancy, and 3 were deaths from other causes. Of the 19 LR, 13 (68%) were DCIS only and 6 (32%) were invasive. Fourteen occurred in the same quadrant and 5 were elsewhere in the ipsilateral breast. The 8-year estimated cumulative incidence of LR was 14.4% (95% CI: 8.4-20.4%). For all other events, the 8-year estimated cumulative incidence was 12.9% (95% CI: 3.6-13.1%).
The estimated annual percentage rates of LR, CBC, and other events were 2.1%, 1.5% and 0.4%, respectively.
Discussion: The results of this prospective study demonstrate a substantial and ongoing risk of LR and CBC in patients with small, nuclear grade 1 or 2 DCIS treated with wide excision with margins of ≥1cm in the absence of RT. Most LRs occurred in the same quadrant, rather than elsewhere in the breast, suggesting that excision alone is inadequate even for this highly selected population. Further study is warranted to determine if there is a subgroup of DCIS patients with nuclear grade 1 or 2 disease who are at low enough risk of LR following wide excision that RT can be omitted safely.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-15-03.