bluuebunny/crossref_metadata_2025_split huggingface dataset:
BRCA testing in underserved women: a qualitative study of intepretations and impacts.
Authors: Joseph G , Wilcox C , Luce J , Beattie MS 
Published: December 2010

Abstract
Abstract #3109
Background: As BRCA testing becomes more available to underserved populations, it is important to understand how the BRCA testing process is interpreted by these patients and their families. It is also essential to study the medical and psycho-social effects of BRCA testing for underserved populations. This study aims to explore the impact of BRCA results and the process of BRCA testing in underserved women.&#x2028; Methods: Underserved women at San Francisco General Hospital (SFGH) who underwent BRCA testing received individual, in-depth, 1-2 hour, semi-structured interviews by a medical anthropologist. Interviews addressed: personal background, initial referral, delivery of test results, understanding of test results, sharing of test results and impact of testing and results on the patient and her family. Interviews were transcribed verbatim, coded using a qualitative data analysis system (Atlas-ti), and analyzed by two authors. Participants were chosen to include the diverse range of patients at SFGH.&#x2028; Results: Of 130 women at SFGH who received BRCA testing, 8 to date have been interviewed (age 35-56). Four had breast cancer. BRCA results include: 4 negative, 2 variant, and 2 positive. Six participants were white; 2 African American. Preliminary data analysis shows that the idea of genetic testing and counseling for breast cancer was completely new at the time of referral for most participants. Participants with breast cancer wanted testing for their children and siblings. "I definitely wanted to know…so that we would have information as far as my son and my sister, and we would have a heads up and know, because early detection is what saved my life." Participants who did not have cancer but who perceived a lot of cancer in the family were interested in and reassured by the genetic counseling/testing experience. “I've been held captive with the word “cancer” all my life." Those with inconclusive results (uninformative negative and variant) had a limited understanding of the implications of their test results for their cancer risk and that of their relatives and struggled with what to communicate to family members. An affected women with negative results said, "With my sister …we have the same parents, but if mine came back negative, I don't know if that means she's totally out of the dark for herself." Participants consistently had positive feelings about their experience with genetic counseling and testing.&#x2028; Conclusions: Given our sample size and methodology, it is not appropriate to generalize. But, this preliminary data suggests that many variables relate to individual understanding and interpretation of BRCA results including: cancer diagnosis and health status at time of testing; BRCA result; experience with counseling; and time since counseling and BRCA testing to process and interpret results.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3109.
Incidence of postmenopausal symptoms and current mamagement: a survey of 260 breast cancer patients.
Authors: Petrella T , Fralick J , Dranitsaris G , Clemons M , Gandhi S , Verma S , Dent R 
Published: December 2010

Abstract
Abstract #3117
Background: The advent of newer and more efficacious adjuvant treatments has allowed women to live longer without cancer recurrence. However these treatments often prematurely induce menopause, worsen menopausal symptoms and may have long-term effects on postmenopausal health. The objectives of this study were to examine the incidence of post-menopausal symptoms and how such symptoms are currently being managed outside of a clinical trial setting, in order to better facilitate patient care. Methods: A self-administered questionnaire was completed by 260 postmenopausal breast cancer patients assessing treatment-induced side effects, how patients were monitored and patient follow-up. Descriptive statistics were used to describe results. Parametric and non-parametric inferential statistics were used in an exploratory analysis to compare post-menopausal symptoms between patient subgroups. Results: Of the 260 patients, 48% percent received endocrine therapy, 17.7% received chemotherapy and 26.2% were not on any therapy at the time of this study. The most common reported symptom was hot flashes (49.2%). Other common reported symptoms were difficulty sleeping (44.6%), weight gain (35.9%), memory problems (33.1%), and vaginal dryness (32.7%). Statistically significant correlations were identified between the use of aromatase inhibitors and the development of hypercholesterolemia and osteopenia. In contrast, the use of tamoxifen was significantly associated with the occurrence of vaginal symptoms such as dryness, itching and bleeding. Majority of patients were also monitored by their family physician with cholesterol monitoring (84%) and bone densitometry (68.1%) either yearly or every two years. Though most patients (83.5%) felt that their medical oncologist should monitor their breast cancer, they preferred to discuss their endocrine symptoms with their family physician (57.9%). Conclusions: The incidence and association of symptoms reported were consistent with the current literature. The management of long-term consequences of breast cancer therapies is going to remain a major part of our role as medical oncologists. However, involvement of family physicians in management of symptoms seems to be preferred by many patients.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3117.
A phase I, dose escalation study of lapatinib in combination with carboplatin, paclitaxel, with and without trastuzumab in patients with metastatic breast cancer.
Authors: Storniolo A , Rubin P , Magrinat G , Parker B , Rush-Tayler A , Sheidler V , Aranjo S , Shaw C , Eldreth N , Lott G , Brechlin J , Loftiss JI , Fleming RA , Weber BL 
Published: December 2010

Abstract
Abstract #3121
Background: Lapatinib is a selective and highly potent dual, competitive inhibitor of erbB1 and erbB2 tyrosine kinases with clinical activity in erbB2-positive metastatic breast cancer (MBC). The combination of carboplatin, paclitaxel, and trastuzumab has been shown to have significant clinical activity in MBC as well as in the adjuvant setting. Given the synergy of dual inhibition with trastuzumab and lapatinib observed in both the preclinical and clinical settings, we assessed the feasibility, safety, and early clinical activity of paclitaxel, carboplatin, lapatinib with and without trastuzumab in patients (pts) with MBC.&#x2028; Methods: MBC pts previously untreated with trastuzumab or cytotoxic chemotherapy for metastatic or locally recurrent disease were enrolled into either Group (Grp) A (erbB2 positive) or B (erbB2 positive or negative). Escalating doses of lapatinib (planned range of 750-1500 mg/d) were administered in combination with (Grp A) or without (Grp B) trastuzumab (4 mg/kg followed by weekly 2 mg/kg infusions). Paclitaxel (80 mg/m2) and carboplatin (AUC 2 mg/ml*min) were administered on days 1, 8, 15 with cycles repeated every 28 days. Starting doses of lapatinib were 750 mg in Grp A and 1000 mg in Grp B. A standard 3 + 3 Phase I design is being used until the optimally tolerated regimen (OTR) dose level is determined. An additional 14 - 17 pts will be enrolled into each grp at the OTR dose level to further assess safety and tolerability.&#x2028; Results: Fourteen pts (Grp A n=8, Grp B n=6) have been enrolled in the study (median age 42 yrs, range 27-66). A median of 5.5 cycles (range 4-17) in Grp A and 3.5 (range 1-7) in Grp B have been administered. All pts had at least one adverse event (AE). In Grp A, grade 3 toxicities include neutropenia (50%), diarrhea (38%), rash (25%), vomiting (13%), hypokalemia (13%), and syncope (13%). No grade 4 toxicities were reported. In Grp B, grade 3 toxicities include fatigue (33%), hyponatremia (17%), menorrhagia (17%), dermatitis (17%), and rash (17%). One pt (in Grp B) had grade 4 neutropenia. No febrile neutropenia was observed. In Grp A, there was one DLT (Gr 3 diarrhea) at lapatinib 1000 mg. In Grp B, one DLT (Gr 4 neutropenia) at lapatinib 1000 mg has been observed. Clinical activity to date includes 8/8 objective responses in Grp A, (1 CR, 7 PR) and 2/6 objective responses (2 PR) in Grp B (all pts in Grp B were erbB2 negative). Dose escalation continues in both grps.&#x2028; Conclusions: Lapatinib may be administered safely in combination with carboplatin, paclitaxel, with and without trastuzumab at known effective doses for each. Clinical activity has been observed.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3121.
Antitumor activity, and antiangiogenic activity of nanoparticle albumin-bound nab-rapamycin in combination with nab-paclitaxel.
Authors: Desai N , Ran S , Volk L , Stutzman A , D'Cruz O , Trieu V 
Published: December 2010

Abstract
Abstract #3125
Background: Rapamycin inhibits downstream signals from the mammalian target of rapamycin (mTOR), a known kinase member of a signaling pathway that promotes tumor growth. Rapamycin's poor aqueous solubility and poor chemical stability have limited its development as an intravenous (IV) anticancer agent. Nab-rapamycin utilizes the albumin-bound technology to allow for IV administration of rapamycin and has demonstrated dose-linear pharmacokinetics and safety up to 90 mg/kg with effective antitumor activity at 40 mg/kg against a human panel of tumor xenografts. This study investigated the efficacy of combined therapy with nab-paclitaxel (Abraxane®) utilizing invasive human breast (MDA-MB-231) and colon (HT29) cancer xenograft models.&#x2028; Material and Methods: Xenograft transplants using luciferase-tagged MDA-MB-231 cells were implanted into mammary fatpad of SCID mice and allowed to reach 460 mm3 in size prior to IV administration of saline (vehicle, n = 9); nab-rapamycin, 3x wkly for 2 wks at 40 mg/kg (nab-rap-2W; n = 8); nab-rapamycin, 3x wkly for 4 wks at 40 mg/kg (nab-rap-4W; n = 8); Abraxane, qdx5 at 30 mg/kg (ABX; n = 8); nab-rap-2W + ABX (n = 9); or nab-rap-4W + ABX (n = 8). HT29 xenografts were also treated with nab-rap-4W (n = 8) and nab-rap-4W + ABX (10 mg/kg, qdx5, IP, n = 8). The in vivo antiangiogenic effect of nab-rapamycin was evaluated using the standard in vivo chick chorioallantoic membrane (CAM) assay with 3-day old embryos (n = 18).&#x2028; Results: Relative to vehicle controls, nab-rap-2W (P &lt; 0.00011), nab-rap-4W (P &lt; 0.0001), and ABX (P &lt; 0.0001) were effective against MDA-MB-231 tumor xenograft models with tumor growth inhibition (TGI) of 60%, 66%, and 73% respectively. Additive antitumor effects were observed with combination of nab-rapamycin + ABX with TGI of 81% and 86% for nab-rap-2W + ABX and nab-rap-4W + ABX groups, respectively. For HT29 tumors, the combination of ABX and nab-rapamycin also showed greater TGI (89%) compared to nab-rapamycin alone (81%). In the chick CAM assay, nab-rapamycin demonstrated antiangiogenic efficacy at doses of 10 µg and above without affecting embryo viability.&#x2028; Conclusions: Combination therapy of nab-rapamycin and Abraxane was more effective at inhibiting breast and colon xenograft tumor growth than single therapy of either drug. The enhanced antitumor activity seen with combined nab-rapamycin-Abraxane may in part be due to the observed antiangiogenic activity of nab-rapamycin.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3125.
Survival of patients with HER2+ metastatic breast cancer and use of trastuzumab following progression: analysis of RegistHER.
Authors: Rugo H , Kaufman P , Tan-Chiu E , Ulcickas Yood M , Paik S , Yardley D , Brufsky A , Mayer M , Birkner M , Wang L , Brammer M , Tripathy D 
Published: December 2010

Abstract
Abstract #3142
Background: Most HER2+ metastatic breast cancer (MBC) patients who initially respond to trastuzumab (T)-based therapies will experience disease progression (PD). Standard practice is to discontinue the cytotoxic agent on which disease progressed, however there is evidence that tumors may remain sensitive to HER2 targeting and that there may be a potentiating effect of T on chemotherapy. We examined the treatment history of a large population of HER2+ MBC patients to assess outcomes associated with continuation of T beyond PD.&#x2028; Methods: This analysis was carried out on patients enrolled in registHER, a prospective observational study of 1023 patients with newly diagnosed (within 6 months) HER2+ MBC. Median f/u from MBC diagnosis is 25 months at the time of data cut-off (12/31/07). For those treated with T prior to first PD, we compared demographics and baseline tumor characteristics for those patients treated with or without T following first PD. Treatment with T was defined as a minimum of 21 days of therapy prior to PD. In addition, we evaluated time to second PD, and overall survival post PD (both endpoints calculated from initial PD). Overall survival (OS) was also calculated from the date of treatment initiation to death for the entire treated cohort.&#x2028; Results: Of 1023 evaluable patients, 873 (85%) were treated with any T-based first-line therapy. 622 T-treated patients progressed and 500 were subsequently treated with T following first PD. Patients who received T post first PD tended to be younger (&lt;50 years of age, 45.2% vs 29.5%) and have hormone receptor positive disease (51.4% vs 42.0%) compared with patients who did not receive T post first PD. Among all treated patients the median overall survival was 35.6 mo (25th-75th-ile:18.6-63.1 mo). Median survival post PD in the 500 patients treated with trastuzumab following first PD was 21.2 mo (25th-75th-ile:11.8-35.8mo).&#x2028; Conclusions: OS in patients on the prospective observational study registHER is longer than the OS of 25.1 months noted in the pivotal trial of first-line HER2+ MBC patients treated with T plus chemotherapy. We will present data on the association between various pre- and post-treatment factors, including the use of T beyond PD, and PFS and OS. This will include a multivariate analysis that specifically examines the association between T use in later lines and survival.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3142.
A novel HER2 inhibitor TAK-285 overcomes trastuzumab resistance of HER2-over-expressing breast cancer.
Authors: Hayashi A , Tamura T , Yusa T , Takagi S , Ohta Y 
Published: December 2010

Abstract
Abstract #3143
Background: The anti-HER2 antibody trastuzumab has been proven highly effective in the treatment of HER2-expressing breast cancers clinically. However, the continuous administration often leads to drug resistance, the mechanism of which is not well understood. Here we present a new mechanism for trastuzumab-resistance. We also show TAK-285, a novel small molecule HER2/EGFR kinase inhibitor under clinical evaluation, overcomes the resistance to trastuzumab.&#x2028; Methods: A trastuzumab-resistant sub-clone (BT-474TR) of the HER2-positive human breast cancer line, BT-474, was established in house by serial passage in the presence of 5 μg/mL trastuzumab for over 5 months. Gene expression profiles of the clones were assessed using Affymetrix HG-U133 plus 2.0 human gene arrays and confirmed by real-time PCR. Target genes were depleted by siRNA-mediated knockdown and confirmed by real time-PCR and immunoblot. Effects on cell growth were assessed by the CellTiter-Glo luminescent cell viability assay (Promega).&#x2028; Results: BT-474TR cells exhibited modified expression of several genes including cofilin, compared to the parental BT-474 cells. Although immunoblotting using anti-cofilin antibody revealed no clear change in protein level, BT-474TR displayed significant increase in phosphorylation of cofilin. Gene-specific knockdown of cofilin-1 led to re-sensitization of BT-474TR to trastuzumab, though the cofilin-2 knockdown did not. Likewise, knockdown of either LIMK1 or PAK1, known to regulate cofilin-phosphorylation, resulted in similar re-sensitization of BT-474TR to trastuzumab. BT-474TR also exhibited increase in phosphorylation of both LIMK1 and PAK1. TAK-285 showed almost equivalent inhibitory activity against both BT-474 and BT-474TR proliferation in cell culture and in xenograft study, while trastuzumab did not affect the proliferation of BT-474TR in either condition&#x2028; Conclusions: These data suggest that activation of cofilin signaling pathway is a probable mechanism of trastuzumab resistance. PAK1/LIMK1/cofilin-1 inhibitors might therefore be useful in preventing or reversing trastuzumab resistance. The phosphorylation status of PAK1/LIMK1/cofilin might also serve as a biomarker of Trastuzumab-sensitivity. Moreover a novel HER2 inhibitor, TAK-285, might show benefit in the treatment of trastuzumab-resistant HER2-expressing breast cancers.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3143.
Incidence of hormone-receptor negative and basal type breast tumors among HLA-A2+ patients and possible implications for cancer vaccine trials: U.S. Military Cancer Institute clinical trials group study I-01, I-02, I-03, and I-04.
Authors: Holmes JP , Benavides LC , Gates JD , Mittendorf EA , Ponniah S , Peoples GE 
Published: December 2010

Abstract
Abstract #3153
Background: Breast cancer prognosis is significantly impacted by expression levels of steroid hormone receptors for estrogen (ER) and progesterone (PR), as well as HER2/neu, a member of the epidermal growth factor receptor family of tyrosine kinases. Recent advances in molecular typing of breast tumors have defined a poor risk subtype of tumor called basal cell. These basal cell breast tumors are “triple negative,” meaning ER and PR negative, and none to low HER2/neu expression (immunohistochemistry [IHC] 0, 1+, or 2+ tumors). Basal cell tumors have a poorer prognosis and do not respond to conventional hormonal or targeted therapy aimed at HER2/neu overexpressing tumors (IHC 3+). Our Cancer Vaccine Development Program (CVDP) has performed several phase I and II clinical trials using immunogenic peptides from the HER2 protein to include E75, GP2, and AE37. Here we present data analysis of ER, PR, and basal cell tumors in HLA-A2+ and A2- patients. Methods: Vaccine trials utilizing E75, GP2, and AE37 were performed separately with similar designs targeting patients with all levels of HER2 expression (IHC 1-3+). Upon completion of standard breast cancer therapy and prior to HLA-typing, disease-free patients were enrolled in the various vaccine trials. HLA-A2 status was determined via flow cytometry of peripheral blood mononuclear cells as E75 and GP2 are HLA-A2+ restricted whereas AE37 is a promiscuous HLA Class II binder. Standard demographic data (including ER, PR and HER2/neu status) were collected, and patients vaccinated according to their respective trial protocol. Data from all trials were pooled for this analysis. Results: To date, of 254 patients enrolled in the trials 54.3% (n=138) were HLA-A2+. Age, tumor size and nodal status were similar between the A2+ and A2- patients. Significantly more A2+ patients had hormone receptor negative (ER-PR-) tumors (n=49) compared to A2- patients (n=27) (35.5% vs. 23.3%; p= 0.03). There was a trend towards increased basal cell tumors among A2+ patients compared to A2- (15.2% vs. 9.5%; p=0.17). Conclusions: Across these clinical trials conducted by the CVDP, HLA-A2+ patients have an increased incidence of ER-PR- tumors and trend toward increased basal cell tumors. ER-PR- and basal cell tumors have a worse prognosis and fewer treatment options than ER+PR+ tumors. As previously reorted, peptide vaccines targeting the HER2/neu protein are safe and effective in eliciting an immune response in patients with tumors expressing various levels of HER2/neu,to include the low levels associated with basal cell tumors. Therefore, peptide cancer vaccines may provide an excellent adjunctive to current treatment for basal cell tumors.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3153.
A phase II study of trastuzumab-DM1, a first-in-class HER2 antibody-drug conjugate, in patients with HER2+ metastatic breast cancer.
Authors: Vukelja S , Rugo H , Vogel C , Borson R , Tan-Chiu E , Birkner M , Holden SN , Klencke B , O'Shaughnessy J , Burris HA 
Published: December 2010

Abstract
Abstract #33
Background&#x2028; Trastuzumab-DM1 (T-DM1), an antibody drug conjugate (ADC) designed to combine the biological activity of trastuzumab with the targeted delivery of a highly potent anti-microtubule agent (DM1) to HER2-expressing cells, has demonstrated activity in a Phase I study. The maximally tolerated dose (MTD) for T-DM1 given every 3 wks was 3.6 mg/kg.&#x2028; Methods&#x2028; This is a multi-institutional, open-label, single-arm, Phase II study of T-DM1, 3.6 mg/kg administered by IV infusion every 3 wks, to pts with HER2+ MBC; 100 efficacy-evaluable pts who have progressed on prior T and chemotherapy given in the metastatic setting will be enrolled. The primary objective is to assess objective response rate (ORR) and safety and tolerability in this patient population. Key secondary objectives include measurement of duration of objective response and progression-free survival; to characterize the pharmacokinetics of this T-DM1 regimen; and to assess the formation of antibodies to T-DM1. A preplanned, protocol specified interim analysis of efficacy data was performed after the first 30 efficacy evaluable pts had completed 4 cycles (12 wks) of treatment. A final analysis will be conducted 26 wks after the last patient has been enrolled.&#x2028; Results&#x2028; As of June 6, 2008, 92/100 pts have been enrolled. Demographic data from the first 31 enrolled pts include: median age 57 (range 38-79); PS 0-1, 29; PS 2, 2; median number prior metastatic chemo agents 2 (range 1-9); median duration of prior T is 76.1 wks (range 12-379); 13 pts (42%) received prior lapatinib. Of the 31 pts, 30 were evaluable for efficacy per protocol. Based on investigator assessments, 12/30 (40%) pts have had a partial (11) or complete (1) response reported. The IRF has reported a partial response in 9/30 (30%) pts to date. To date, these 31 pts have received a median of 4 T-DM1cycles (range 1-11). Gr2 adverse events (AEs) include thrombocytopenia (10%), fatigue (13%), nausea/vomiting (10%), infusion reaction/fever/chills (10%). Gr3 thrombocytopenia occurred in 10% of pts and Gr4 AEs occurred in 2 (6%) pts (thrombocytopenia and transaminase elevation). Sixteen (52%) pts have discontinued therapy, 11 for progressive disease.&#x2028; Conclusions&#x2028; T-DM1 has shown single-agent clinical activity in pts who have progressed on prior HER2-directed therapy. The safety profile of T-DM1 appears tolerable at the recommended dose. To date, preliminary data show a 40% investigator-determined response rate and a 30% IRF-reported response rate. Updated results for the entire study population will be presented.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 33.