bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting Axillary Lymph Node Status Using Preoperative Ultrasound-Guided Fine Needle Aspiration Cytology of Radiologically Equivocal and Abnormal Nodes.
Authors: White J. , Hogan B. , Langlands F. , Dall B. , Horgan K.
Published: December 2010

Introduction:The superiority of ultrasound (US) over clinical examination in the assessment of axillary nodes in patients with breast carcinoma is well recognised. Fine needle aspiration cytology (FNAC) is a quick and minimally invasive procedure to determine the status of axillary lymph nodes pre-operatively. Sentinel lymph node biopsy (SLNB) is now widely accepted as the primary axillary staging procedure in the management of early breast cancer. A negative SLNB obviates the need for more extensive axillary surgery, thereby reducing the morbidity associated with axillary node clearance (ANC) in patients with node negative breast cancer. Patients with a SLNB positive for metastasis usually require further axillary treatment, which may include completion ANC and/or radiotherapy. Improving the accuracy of pre-operative staging is desirable in reducing the number of completion ANC procedures necessitated following positive SLNB. The aim of this study is to assess the accuracy of pre-operative US-guided FNAC of radiologically equivocal or abnormal axillary lymph nodes.Method:Patients with a diagnosis of invasive breast carcinoma underwent axillary US. Those with radiologically equivocal or abnormal nodes had US-guided FNAC. Patients with a metastatic FNAC had ANC, whereas those with insufficient (i.e. no lymphocytes seen on cytology), benign or equivocal FNAC had SLNB.Results:Correlation of FNAC result and final histologyFNAC ResultN=59Node positivity N=42Inadequate54Benign173Equivocal10Suspicious11Malignant3534 The positive predictive value of suspicious or malignant cytology from a radiologically equivocal or abnormal node is 97%. The negative predictive value is 70%. US-guided FNAC used in the context has 83% sensitivity and 94% specificity.Of the five patients with radiologically equivocal or abnormal nodes and an inadequate cytology (no lymphocytes seen), four had a metastatic sentinel node biopsy.One patient had a malignant FNAC prior to neoadjuvant chemotherapy (NACT) and had benign histology on subsequent ANC. If this patient is excluded from analysis, the positive predictive value rises to 100%.Conclusion:US-guided FNAC of radiologically equivocal or abnormal axillary lymph nodes accurately predicts node positivity and can be used to avoid an unnecessary SLNB procedure.Inadequate FNAC from an equivocal or abnormal node is not sufficient evidence to recommend SLNB rather than ANC as the initial surgical axillary procedure. Patients with such findings should have a repeat US-guided FNAC before choosing to proceed with SLNB.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1031.
Non-Sentinel Lymph Node Status of Patients with T1/T2 Breast Cancer and Micrometastasis in the Sentinel Lymph Node.
Authors: Reitsamer R. , Glueck S. , Menzel C. , Peintinger F.
Published: December 2010

Background: Micrometastatic disease in the sentinel lymph node is still an indication for complete axillary lymph node dissection. To further reduce morbidity in breast cancer patients the omission of complete axillary lymph node dissection in patients with micrometastasis in the sentinel lymph node would be desirable.Methods: We retrieved our data-base and looked for the non-sentinel lymph node status in patients with micrometastasis in the sentinel lymph node.Patients with primary T1/T2 breast cancer and sentinel lymph node biopsy were examined for their sentinel lymph node status. Patients with a micrometastasis in the sentinel lymph node, who received a complete axillary lymph node dissection were eligible for evaluation. Patients with a micrometastisis in the sentinel lymph node, who did not receive complete axillary lymph node dissection and patients after primary systemic therapy were excluded.Results: 103 patients were eligible for evaluation. All patients had micrometastases (0,2 to 2,0mm) in the sentinel lymph nodes. In total 15/103 patients (14.6%) had a further metastasis in one or two non-sentinel lymph nodes. 8/103 patients (7.8%) had one macrometastasis in a non-sentinel lymph node with sizes from 2.1mm to 5.0mm. 3/103 patients (2.9%) had a micrometastasis in two non-sentinel lymph nodes and 4/103 patients (3.9%) had one micrometastasis in one non-sentinel lymph node.Mean age of the patients was 57 years, 34 (33%) being premenopausal and 69 (67%) being postmenopausal. 22 patients (21.4%) received immediate axillary dissection after sentinel lymph node biopsy, but 81 patients (78.6%) had a secondary axillary lymph node dissection after the final pathological report. In 19 patients (18.4%) the micrometastasis in the sentinel lymph node could be detected by frozen sections, in 77 patients (74.8%) by serial sections at 250µm in the paraffin embedded sentinel lymph node and in 22 patients (21.4%) by immunohistochemistry only.Discussion: As long as we are lacking reliable methods for predicting the non-sentinel lymph node status for patients with micrometastases in the sentinel lymph node, and as long as the impact of micrometastases in the axilla are subject of debate, axillary lymph node dissection should be performed after sentinel lymph node biopsy with micrometastases in the sentinel lymph node.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1034.
Preventive Effects of Lapatinib, a Combined EGFR 1 and EGFR 2 Inhibitor, on Methylnitrosourea-Induced ER+ and MMTV-Neu/P53 KO ER- Mammary Cancers.
Authors: Lubet R. , Bode A. , Juliana M. , Steele V. , Grubbs C.
Published: December 2010

Lapatinib is a small molecule TK inhibitor that blocks both EGFR 1 and EGFR 2 (Neu) in the nanomolar range. While the potential usefulness of this agent in Neu over-expressing tumors appears obvious, its potential efficacy in ER+ tumors that do not over-express Neu seems more problematic. The efficacy of lapatinib was tested in two animal models of mammary cancer; the MNU induced rat model that has ER+ mammary cancers and the MMTV-Neu/P53 KO transgenic mouse model that has Neu over-expressing ER- cancers. In the ER+ mammary model, the carcinogen (75 mg/kg BW) was administered to female Sprague-Dawley rats at 50 days of age via the jugular vein. These animals subsequently developed multiple well-differentiated mammary adenocarcinomas. Lapatinib treatment (75 or 25 mg/kg BW/day), 7x/week by gavage, was initiated five days after the carcinogen and continued until the end of the study (148 days post MNU). The high and low doses of lapatinib reduced mammary cancer multiplicity by 81% and 31%, respectively. Lapatinib at the higher dose was also an effective therapeutic agent in this model. In the MMTV-Neu/P53 KO model (over-expressed Neu under control of MMTV and heterozygous KO of P53), it was observed that lapatinib administered at a dose of 75 mg/Kg BW/day beginning when an animal was 8 weeks of age reduced cancer multiplicity by 60 %. When the short term effects of lapatinib was examined in both models, it was found that levels of phosphorylated EGFR 1 and 2, ERK and AKT, as well as the proliferation index (Ki 67), were reduced in the cancers in both models. The potential use of an agent such as lapatinib in preventing ER+ tumors is of particular interest since tamoxifen and to a lesser degree aromatase inhibitors are relatively ineffective in the prevention of ER+ tumors which over- express Neu. Supported by NCI contract HHSN261200433001C.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1043.
Is Metabolic Syndrome and Central Obesity Relevent to Biology and Progression of Postmenopausal Breast Cancer?
Authors: Healy L. , Ryan A. , Carroll P. , Ennis D. , Boyle T. , Kennedy M. , Connolly E. , Reynolds J.
Published: December 2010

Introduction: Obesity isassociated with both an increased risk of postmenopausal breast cancer and increased mortality rates. The mechanism is unclear, and central (visceral) obesity, insulin resistance, altered sex steroids, and altered adipokines, are mooted as possible factors. These features may cluster in the so-called Metabolic Syndrome (MetS), and the focus of this study was to systematically relate MetS to standard clinicopathological indices of breast cancer.Methods: Postmenopausal women with newly diagnosed breast cancer (n=105) were prospectively recruited. A detailed clinical and dietary history was performed, as well as body composition analysis, metabolic screen, and plasma measurement of adipokines and inflammatory markers. MetS was defined according to the International Diabetes Federation definition.Results: One hundred and five patients were recruited, the median age was 68 years (40-94) and the mean BMI was 28.3 ± 5.2 kg/m2, with 87% of patients centrally obese. MetS was diagnosed in 39% of patients, and was significantly (p<0.005) associated with 13cm greater waist circumference, higher total and trunk fat mass and increased inflammation with CRP levels almost double for MetS patietns compared to non MetS (10.3 ± 2.7 V's 5.8 ± 1.0 mg/L; p=0.084).Patients with later pathological stage (II- IV) were significantly more likely to be obese (BMI) (45% Vs 16%; p=0.007), centrally obese (waist circumference) (94% Vs 72%; p=0.009), hyperglycaemic (31% Vs 12%; p=0.047), hyperinsulinaemia (19% Vs 0; p=0.026) and 51% had MetS compared to 12% for early stage disease (Path stage 0-I). Patients with node positive disease were significantly more likely to be hyperinsulaemic (22% V's 5%; p=0.030) and have MetS (50% V's 30%; p=0.028) than node negative disease.MetS was not associated with hormone receptor status or serum levels of oestradiol, progesterone, testosterone, or SHBG levels. However, SHBG levels decreased with obesity (p=0.002) and as the number of features of MetS increased (0 features: 87 ± 15.8 compared to 5 features: 32 ±2.7; p=0.003). Insulin levels increased with obesity (p=0.006), and with increasing number of features of MetS.Discussion: MetS and central obesity are common in Irish postmenopausal breast cancer patients. MetS appears to be associated with aggressive tumour biology, and this may have significance in preventive and novel treatment approaches.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1051.
Burden of Sexual Dysfunction in Women with Breast Cancer.
Authors: Goldfarb S. , Dickler M. , Fruscione M. , Sit L. , Jia R. , Kaplan J. , Barz T. , Atkinson T. , Hudis C. , Basch E.
Published: December 2010

Background: Sexual dysfunction is reported after chemotherapy and endocrine therapies, and causes a substantial burden on women with breast cancer. However, the prevalence and severity of sexual dysfunction in women undergoing therapy for both local and metastatic disease is not well defined. Improved understanding of sexual dysfunction may facilitate enhanced treatment and interventions in patients with breast cancer undergoing active treatment, and in survivors of this disease.Methods: We developed a survey that includes a previously validated questionnaire, the female sexual function index (FSFI), as well as an established measure of health-related quality of life (the EuroQol EQ-5D), and disease-specific items to characterize sexual dysfunction and its causes based on literature review and expert consultations. Anonymous administration of the surveys was conducted in outpatient clinic waiting areas of the Breast Cancer Center at Memorial Sloan-Kettering Cancer Center (MSKCC) and two community centers, under an IRB waiver of consent.Results: During November 2008 through May 2009, 509 women undergoing treatment for breast cancer of all stages were each queried once. The mean age was 51 (range 26-91). 87% reported current or past hormonal treatment, and 82% reported current or past chemotherapy (76% adjuvant; 24% for metastatic disease). Sexual dysfunction attributed to breast cancer or its treatment, defined as an FSFI score <26, was reported by 76% of respondents. Among these women, 316/386 (82%) patients considered their sexual symptoms to be bothersome, with 247/386 (64%) noting moderate or severe levels of bother (score >=5/10). Patients attributed their sexual dysfunction to chemotherapy in 318/373 (85%) of cases; to hormonal therapy in 221/298 (74%) of cases; and to surgery in 331/442 (66%) of cases. Other reported contributors to sexual dysfunction include a new diagnosis of breast cancer by 81% of respondents, anxiety by 82% of respondents, and change in relationship with a partner by 55% of respondents.Conclusion: Sexual dysfunction is prevalent in women treated for breast cancer and should be discussed with patients as a potential adverse effect of therapy. Assessment of sexual symptoms throughout treatment and beyond may facilitate the use of potential interventions such as lubricants, dilators, treatment modification, topical estrogens, and counseling. Future work includes a longitudinal prospective trial to further characterize the etiologies of these symptoms and a randomized controlled trial to evaluate interventions for sexual dysfunction.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1056.
Weight Gain Is Associated with Increased Risk of Hot Flashes in Breast Cancer Survivors on Aromatase Inhibitors.
Authors: Su H. , Su H. , Sammel M. , Springer E. , Freeman E. , DeMichele A. , DeMichele A. , Mao J. , Mao J.
Published: December 2010

Objective: Hot flashes in breast cancer survivors (BCS) receiving adjuvant aromatase inhibitor (AI) therapy are common, but risk factors for these symptoms are not well-defined. This study tested if body size is associated with hot flashes in BCS on AI therapy.Materials and methods: We performed a cross-sectional analysis of a cohort of postmenopausal women with Stages 0-III breast cancer receiving adjuvant AI therapy at a university hospital-based outpatient breast oncology clinic. Subjects provided patient-reported outcomes on hot flashes, current and pre-breast cancer weight and height, and additional demographic and treatment data.The primary outcome was occurrence of hot flashes. Secondary outcomes included hot flash severity and frequency. The exposures of interest were 1) current weight and 2) weight change since breast cancer diagnosis, categorized as weight loss (lost 10 pounds or more), maintenance (+/- 10 pounds), or gain (gained 10 pounds or more). Multivariable logistic regression models examined the independent association between hot flash outcomes and current weight or weight change while controlling for confounders.Results: 300 participants were enrolled at a mean age of 61 years (range 33-86) after mean duration of AI exposure of 23 months (range 1 month-9 years). 177 (59%) reported hot flashes overall, 96 (32%) reported moderate to very severe hot flashes, and 60 (20%) had at least 4 hot flashes daily. 182 (61%) experienced weight maintenance, while 81 (27%) had weight gain and 34 (11%) had weight loss. In a multivariable model, weight gain was independently associated with hot flash occurrence (OR 2.1, 95% CI 1.1-4.4) and hot flash severity (OR 2.4, 95% CI 1.4-4.9), but not hot flash frequency, after adjusting for current weight and height, age, smoking, race, prior chemotherapy and prior tamoxifen therapy. Hot flash occurrence was also significantly associated with current smoking (OR 5.1, 95% CI 1.1-24.0) and age (OR for each additional year of age 0.93, 95% CI 0.90-0.97). Current weight, alcohol use, AI type, and AI duration were not associated with any of the three outcomes.Conclusions: In an outpatient BCS population on AI therapy, weight gain is a risk factor for both hot flash occurrence and severity. Women who gained at least ten pounds since breast cancer diagnosis were two times more likely to have hot flashes than women who maintained or lost weight. These results support the thermoregulatory model of hot flashes and argue against a protective effect of body fat in this population.Support: ACS MRSG-08-110-01-CCE, ACS CCDA#-08-107-01, Pennsylvania Department of Aging

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1059.
Ethnicity, Age, and Employment Associated with Persistent Symptoms in Breast Cancer Survivors.
Authors: Fu O. , Crew K. , Jacobson J. , Greenlee H. , Yu G. , Campbell J. , Ortiz Y. , Hershman D.
Published: December 2010

Background: Increases in breast cancer survival rates have prompted research on the quality of life (QOL) of breast cancer survivors, but relatively few studies have included nonwhite women or women who do not speak English.Patients and Methods: We administered a survey to patients who were ≥3 months post-completion of their adjuvant treatment for stage 0-III breast cancer at Columbia University Medical Center. The questionnaire asked patients about their experience of 16 physical and emotional symptoms in the last 7 days. Univariate analysis was performed to compare differences in each symptom measure by clinical, demographic, and treatment-related factors. Factor analysis is a statistical tool used to describe the covariance relationships among many inter-related variables in terms of a few underlying factors. Maximum likelihood factor analysis of the 16 symptoms using a varimax rotation identified 4 underlying symptom clusters that we termed depression-related, chemotherapy-related, hormone-related, and pain-related based on our clinical impression of the symptom clusters. We then used analyses of variance (ANOVA) to evaluate the associations of each of the sociodemographic and clinical characteristics (race, age, income, education, language, employment, years since diagnosis, and stage) individually with each of the four factors and multiple linear regression analysis to evaluate the associations of all of the sociodemographic and clinical characteristics with each of the four factors.Results: Of 139 patients surveyed, 58 were white, 63 Hispanic, and 18 black. Most women were <5 years post-diagnosis. The symptom most commonly reported was fatigue (76%). The most common severe symptom was muscle aches (40%). Most patients (70%) complained of ≥6 symptoms. Hispanic women were more likely than others to report >10 symptoms (chi2 11.8, df: 4, p<0.05), chemotherapy-related symptoms (beta 1.06±0.465; p<0.05) and pain-related symptoms (beta 0.778±0.362; p<0.05). Unemployed women were more likely than employed women to report chemotherapy-related symptoms (beta 0.472±0.228; p<0.05). Women <45 years old were less likely than women >65 years old to report chemotherapy (beta -0.883±0.364; p<0.05) and pain-related symptoms (beta -0.569±0.283; p<0.05).Conclusions: The majority of women in this population of breast cancer survivors, especially those who were Hispanic, elderly, or unemployed, were burdened by symptoms, most commonly fatigue. As the number of breast cancer survivors increases, and the U.S. population diversifies, it is important to identify, characterize and alleviate perceived post-treatment physical and emotional symptoms in women of different backgrounds.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1064.
Short Term Evaluation of a Comprehensive Post Treatment Rehabilitation Program for Cancer Patients Treated with Curative Intent.
Authors: Hanssens S. , Luyten R. , Blanken W. , Watthy C. , Fontaine C. , Decoster L. , Baillon C. , Trullemans F. , De Grève J.
Published: December 2010

Background: Many physical and psychosocial interventions or combined interventions have been developed for cancer survivors. We implemented a 12- week comprehensive rehabilitation program, combining physical exercise, psycho-education and individual counselling. We hypothesized that the rehabilitation program would lead to improvements in quality of life, fatigue, kinesiophobia, distress, anxiety, depression, physical functioning and physical condition.Patients and methods: A longitudinal cohort study design was applied in 74 cancer survivors. The participants filled out a questionnaire and underwent a physical test at baseline and at the end of the program. Different measurement instruments were used: EORTC QLQ-C30, FACT-F, HADS, RAND-36, TAMPA, Distress Barometer and Tecumseh Step Test. Statistical analysis was carried out using SPSS 17.0.Results: Thirty six patients (48,6%) participated. Drop out was due to following reasons: difficulty to combine the program with job and family, lack of motivation, self sufficiency or alternative method. Eighty five percent of the participants were female and the most prevalent cancer was breast cancer.The overall quality of life improved significantly after the rehabilitation program compared with the baseline assessment (p=0,000). There was significant improvement also in specific aspects such as physical condition (p=0,007), fatigue (p=0,010) and depression (p=0,012). In contrast kinesiophobia (p=0,229), distress (p=0,344) and anxiety (p=0,101) did not change significantly.Discussion and Conclusion: We have initialized and evaluated the short term impact of a comprehensive rehabilitation program as a post treatment effort in cancer patients treated with curative intent. This comprehensive rehabilitation program is the first to include individual counselling and distress measurement. A general and significant improvement in all aspects affecting quality of life and rehabilitation was observed, but less so for aspects that might be influenced by prognostic concerns. The relative contribution of the program versus spontaneous recovery and long term impact need to be further determined in a prospective randomized study.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1065.
Identification of a Prognostic Signature Based on the Expression of Insulin-Related Genes in Early Breast Cancer.
Authors: Gennari A. , Sormani M. , Decensi A. , Decensi A. , Pronzato P. , Mirisola V. , Puntoni M. , Roncella M. , Ghilli M. , Bruzzi P. , Pfeffer U.
Published: December 2010

Background: A substantial body of evidence indicate that the insulin pathway plays a key role in breast cancer development and progression and may represent a therapeutic target, especially in those patients exposed to high plasmatic level of insulin. However, the potential prognostic role of genes related to the insulin-pathway in breast cancer cells has not been explored. With these premises, we evaluated the prognostic role of the expression of genes related to the insulin pathway in early breast cancer. Methods: Candidate genes were selected from published literature, genomic databases, and gene expression profiling experiments performed in insulin resistant subjects, yielding 143 genes that were used to develop a molecular classifier. We used three publicly available breast cancer datasets, GSE1456, GSE3494 and GSE2990 that include gene expression data on a total of 502 cases with clinical follow up. The insulin gene signature was developed on GSE1456, containing microarray data from 159 early breast cancer patients. This dataset was split by a random procedure into a training set and a validation set. Univariate non-parametric Mann-Whitney U test was used to identify genes differentially expressed. Expression of genes significantly correlated with relapse was combined in a linear score. Patients were classified as low or high risk with respect to the median score. External validation was performed on GSE3494 and GSE2990. Results: On the training set, 15 genes resulted differentially expressed in relapsed and non relapsed patients: the 8-year disease free survival (DFS) was 91% (SE =4%) and 51% (SE = 8%) in the high and low risk group (p< 0.001); HR = 10.6 (95% CI 3.2-35.5, p<0.00001). In the validation set, the 8-year RFS was 97% (SE = 3%) and 54% (SE = 10%), respectively (p = 0.009); HR = 4.6 (95% CI 1.01 to 20.7, p 0.04). External validation was performed on two independent datasets, GSE3494 and GSE 2990 including 350 early breast cancer patients. In GSE3494 the 8-year DFS was 72% (SE = 5%) and 61% (SE = 4%) in the high and low risk group (p = 0.03), respectively. In GSE 2990 the 8-year DFS was 74% (SE = 7%) and 55% (SE = 8%), respectively, (p = 0.03). By multivariate analysis, the insulin signature resulted significantly associated with DFS, independently of age, tumor size, ER status, nodal status and grade. Conclusions: Our findings indicate that the insulin pathway is involved in breast cancer prognosis at a genomic level and might provide a better way to individualize therapeutic interventions targeting insulin signaling.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 108.
Final Results of ABCSG-24, a Randomized Phase III Study Comparing Epirubicin, Docetaxel, and Capecitabine (EDC) to Epirubicin and Docetaxel (ED) as Neoadjuvant Treatment for Early Breast Cancer and Comparing ED/EDC + Trastuzumab (T) to ED/EDC as Neoadjuvant Treatment for Early HER-2 Positive Breast Cancer.
Authors: Steger G. , Greil R. , Jakesz R. , Lang A. , Mlineritsch B. , Melbinger-Zeinitzer E. , Marth C. , Samonigg H. , Kubista E. , Gnant M.
Published: December 2010

Background: Since pathological complete responses (pCR) might be a surrogate for effective eradication of micrometastatic disease leading possibly to prolonged overall survival in primary breast cancer, neoadjuvant treatment of early breast cancer aims at achieving high rates of pCR.Methods: Primary aim of ABCSG-24 is to evaluate the influence of 6 cycles of EDC±T (experimental group) as compared to 6 cycles of ED±T (control group) on the rate of pCR at the time of surgery. 536 patients (pts) (268 pts/group, 5% dropout rate for 510 eligible pts, power=83%,p<0.05 (two-sided Chi²-test)) had to be accrued to detect a difference in pCR of 16% (ED±T) vs. 27% (EDC±T). 94 pts (47 pts/group,5% drop-out rate for 90 eligible pts, power=80%,p<0.05,two-sided Chi²-test) of the 536 pts must had a HER-2 positive (pos) tumor to detect a difference in pCR of 20% (ED/EDC)vs. 50% after ED/EDC+T.Between 11/2004 and 11/2008 536 pts with biopsy proven operable breast scheduled for neoadjuvant treatment (except T4d) +/- nodal involvement and without distant disease were stratified and randomized to receive either 6 x EDC every 21 days (day 1:E75 mg/m ² iv and D75 mg/m² iv,day 2:pegfilgrastim 6 mg sq, C: 2 x 1000 mg/m²/day days1-14 orally) or 6 cycles of identical ED without C. Pts with HER2pos tumors were also randomized to T 8mg/kg iv (day1) followed by 6mg/kg q 21 days or to no T.Results: 512 pts are eligible for toxicity and efficacy. In the intention to treat analysis there was no significant difference in the incidence of serious adverse events (EDC:26% vs. ED:21%,p=0,16) but significantly less patients completed the scheduled 6 cycles (EDC:75% vs. ED:97%,p<0.0001). After EDC significantly more pts had documented pCR (EDC:23,8% vs. ED:15,2%;p=0,036). In the HER2pos subgroup (eligible pts: n=90) there was a non-significant (p=0,369) difference in the rate of pCR after ED/EDC+T (40%) vs. ED/EDC (26,7%).Discussion: Neoadjuvant EDC in early breast cancer results in a significantly higher pCR rate than ED. ED/EDC + T leads to a non-significant higher rate of pCR than ED/EDC alone which might be due to a higher observed rate of pCR with ED/EDC alone than the expected. ED/EDC+/-T are feasible for outpatient use but C associated toxicity must be monitored closely and dose reduction rules must be observed.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1081.
Eradication of Axillary Lymph Node Metastases Occurs in 74% of Patients Receiving Neoadjuvant Chemotherapy with Concurrent Trastuzumab for HER2 Positive Breast Cancer.
Authors: Dominici L. , Negron Gonzalez V. , Buzdar A. , Lucci A. , Mittendorf E. , Pusztai L. , Krishnamurthy S. , Le-Petross H. , Babiera G. , Bedrosian I. , Meric-Bernstam F. , Hunt K. , Valero V. , Kuerer H.
Published: December 2010

Background:Administration of neoadjuvant chemotherapy (NCT) can result in a pathologic complete response (pCR) in the breast and axilla which correlates with improved disease-free and overall survival. This study examines the incidence of axillary pCR and the effect of axillary pCR on disease-free survival (DFS) in patients (pts) with HER2 positive disease and biopsy-proven axillary metastases that received trastuzumab-based NCT.Material and Methods:The records of 109 consecutive pts with HER2 positive breast cancer and ultrasound-guided fine needle aspiration (FNA) biopsy-confirmed axillary metastases were analyzed. All pts received trastuzumab-based NCT prior to undergoing breast surgery with complete axillary lymph node (ALN) dissections. After surgery, patients were subdivided into those with and without residual ALN disease. Survival was evaluated by the Kaplan-Meier method.Results:Of patients with documented positive ALNs before chemotherapy, 81 (74%) had an ALN pCR. ALN pCR was not associated with estrogen receptor status, grade, tumor size or age (p=NS). The median number of nodes removed was 19 in the ALN pCR group and 18.5 in the group with residual axillary disease (p=NS). The only significant difference between the groups was that more patients in the ALN pCR group achieved complete pathologic response of disease within the breast (p<0.001) (78% with and 25% without ALN pCR, respectively). At a median follow-up of 29.1 months, DFS in the ALN pCR group (95%) was significantly greater than in the group with residual axillary disease (81%) on Kaplan-Meier analysis (p=0.02).Discussion:Trastuzumab-based NCT results in axillary pCR in 74% of patients with HER2 positive disease. These pts have improved DFS compared with patients with residual disease. The majority of patients with proven axillary metastases will have eradication of disease after treatment with trastuzumab-based NCT, and this has implications for the surgical management of the axilla in these types of pts.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1086.
Lapatinib Can Be Safely Given Concomitantly to EC-Doc as Neoadjuvant Chemotherapy for Breast Cancer. First Planned Safety Analysis of the Geparquinto Study (GBG 44).
Authors: Untch M. , Kaufmann M. , Hilfrich J. , Strumberg D. , Fehm T. , Bischoff J. , Gauwerky J. , Loibl S. , Nekljudova V. , von Minckwitz G.
Published: December 2010

Background:Trastuzumab has significantly improved pathological complete response rates of neoadjuvant treatment in HER2 positive breast cancer (HER2+BC). The tyrosine-kinase inhibitor lapatinib (L) has shown efficacy in metastatic breast cancer. Previous data in metastatic breast cancer suggested increased hematologic toxicity of docetaxel (Doc) combined with L. As the dose and safety of L in combination with epirubicin (E), cyclophosphamide (C), and Doc has not yet been adequately tested, an integrated safety phase was conducted.Patients and Methods:The GeparQuinto trial, a neoadjuvant phase III study, planned to include 2500 patients (pts) in total and 594 HER2+BC pts for comparing L versus trastuzumab (H) given concomitantly to anthracycline-taxane based chemotherapy. Female pts with untreated, histologically confirmed uni- or bilateral, cT3/4a-d, HER2+BC and no clinically relevant cardiovascular co-morbidities received 4 cycles of E (90mg/m²) + C (600 mg/m²) q3w followed by Doc 100mg/ m² q3w. Pts were randomized to receive either H (6 mg/kg; 8mg/kg loading dose; q3w) or L given concomitantly to all cycles. The 1st cohort in the L arm received 1000 mg/d L during the 1st cycle EC and the 1st cycle Doc and 1250 mg/d L through all other cycles and received prophylactic treatment with pegfilgrastim (6 mg on day 2) and loperamide (2x2mg daily). The 2nd cohort received no loperamide, if <=1 diarrhea grade 3 and no pegfilgrastim if <=3 events of grade 4 neutropenia and <=1 febrile neutropenia (FN) occurred during cycles 1+2 of the 1st 10 pts of the 1st cohort. The remaining pts received 1250 mg/d L in the first cycle and no prophylaxis with loperamide if <=2 diarrhea grade 3 and <= 1 diarrhea grade 4 and no pegfilgrastim if <=4 events of grade 4 neutropenia and <=2 FN occurred during cycles 1+2 of the 1st 10 pts of the 2nd cohort. An interim safety analysis was planned when 60 pts completed all cycles.Results:As of June 1 2009 918 (178 HER+BC) pts have been recruited. 31 pts received ECH-DocH and 29 pts ECL-DocL. In the 1st cohort no grade 3 diarrhea and 2 grade 4 neutropenias occurred. In the 2nd cohort again, no grade diarrhea 3, but 8 grade 4 neutropenias (1 FN) occurred in 4 pts. L was, when compared to H, associated with less grade 1/2 anemia (27.6% vs. 51.6.%) but more grade 1/2 skin rash (27.6% vs. 6.5%) during cycle 1 (data on all cycles will be presented). No significant differences for other toxicities were seen.Conclusion:L at a dose of 1250 mg/d is feasible and well tolerated when given concomitantly to EC-Doc if G-CSF is given prophylactically during DocL.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1094.
Phase II Trial of Neoadjuvant Pegylated Liposomal Doxorubicin with Paclitaxel and Trastuzumab in Patients with Operable Her2-Positive Breast Cancer.
Authors: Hyams D. , Leichman G. , Klein P. , Rietchsel P. , Levine E. , Gebski V. , Kelley M.
Published: December 2010

Background: Doxorubicin, paclitaxel and trastuzumab are among the most active agents used in the treatment of Her2-positive invasive breast cancer. However, trastuzumab is associated with cardiotoxicity that is significantly amplified in the presence of doxorubicin. Pegylated liposomal doxorubicin (PLD) has been reported to have greatly reduced cardiotoxicity when compared to native doxorubicin. This pilot study was designed to assess safety and efficacy of concurrent PLD, paclitaxel (TAX), and trastuzumab in the preoperative setting.Methods: Eligible patients included women with T1c-T4, N0-1, M0, Her2-positive invasive breast cancer who had received no prior treatment. The treatment regimen consisted of concomitant PLD 24 mg/m2 or 20 mg/m2 (14pts/10pts) q 3 weeks, TAX 80 mg/m2 weekly, and trastuzumab 2mg/m2 weekly after an initial 4 mg/m2 loading dose, for a total of 18 weeks. MUGA scans were obtained at baseline, after 9 weeks, and after 18 weeks prior to surgery. The primary endpoint was pathologic complete response (pCR).Results: Twenty-four patients were entered on study. The median age was 55 (range 30-72). One subject had AJCC Stage I disease, 14 subjects had Stage II disease, 9 subjects had Stage III disease, and the median pre-treatment tumor size was 4.5 cm (1.2 cm-10.0 cm). Twelve subjects required dose reductions of PLD, 9 required dose reduction of TAX, and 5 discontinued therapy early. One subject withdrew during the 1st cycle, and 1 patient died due to an event unrelated to the investigational treatment. Thirteen of the 22 evaluable subjects had pCR (59%), 9 subjects had PR (41%). The principal treatment-related toxicity was Grade II or III skin toxicity in 18 of 24 subjects (75%). No overt cardiotoxicity was noted, with the mean change between pre-treatment and pre-surgical MUGA of -.25% (range -12-7%).Discussion: The combination of PLD, TAX, and trastuzumab given every 3 weeks, appears to be a highly effective regimen, without evidence of increased cardiotoxicity. However skin toxicity is prominent and may be exacerbated by a previously reported effect of TAX on PLD pharmacokinetics. Further investigation of this highly effective regimen should focus on reducing skin toxicity, while maintaining efficacy.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1098.
Clinical Advantages of Neoadjuvant Docetaxel (T) and Carboplatin (C) ± Trastuzumab (H) in Locally Advanced Breast Cancer (LABC).
Authors: Chang H. , Glaspy J. , Gornbein J. , Kass F. , Allison M. , Chung D.
Published: December 2010

Background: Neoadjuvant systemic treatment has become a standard choice for locally advanced breast cancer with many proposed benefits in achieving clear margins, preserving breasts, reducing relapse and improving survival. Recently, we completed a neoadjuvant trial studying the effects of 4 cycles of docetaxel (75 mg/m2) and carboplatin (AUC=6) with or without trastuzumab (4mg/kg loading dose and 2 mg/kg weekly dose) on LABC. In this report, we assessed whether clinical complete response (cCR) or pathologic complete response (pCR) correlated better with having breast conservation surgery, fewer relapses and improved survival outcomes.Materials and Methods: Seventy-one of the 74 consented patients with T2-T4 non-metastatic breast cancer completed the preoperative treatment and had evaluable data on tumor response, surgical treatment and clinical outcome. We used the Kaplan Meier method to estimate survival probabilities and log rank test to compare relapse-free and survival curves.Results: Clinical outcomes from a preplanned 2-year analysis of a phase II neoadjuvant are reported. Of the 19 patients with pCR, 16 occurred in patients with cCR (n=32) and 3 were in the group of non-cCR (n=39). Although cCR overestimated tumor response, 84.2% pCR occurred in the cCR group and only 15.8% in the non-cCR group. The relapse-free survival at 2 and 3 years for pCR vs. non-pCR were 93.8% and 83.3% vs. 78.4% (p=0.122) and 58%, respectively; and for cCR vs. non-cCR were 80.9% and 65% vs. 83.9% and 64.3% (p=0.999). The pCR was also more predictive than cCR for overall survival. Of the 30 HER2 positive breast cancer, 15 received trastuzumab throughout the neoadjuvant and adjuvant phases for a total of 52 weeks. The remaining 15 patients received identical chemotherapy but trastuzumab was started after the surgery and continued for 52 weeks. While distinctively different pCR between the two treatment groups was expected, the better survival rate observed in the group receiving neoadjuvant TCH was not expected. Our study showed that pCR was strongly associated with a more frequent use of lumpectomy than the non-pCR group 63.2% vs. 36.5% (p=0.045).Conclusion: The effects of preoperative systemic treatment on LABC can be assessed both clinically and pathologically. Our data suggests that pathologic complete response was a better predictor for having breast conservation surgery and relapse-free survival rates. Our data also suggests that patients with HER2 positive breast cancer may benefit from receiving preoperative trastuzumab and chemotherapy.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1100.
Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer: Pathologic Complete Response and Survival after Long-Term Follow-Up.
Authors: Guiu S. , Arnould L. , Coudert B. , Liégard M. , Mayer F. , Favier L. , Fumoleau P.
Published: December 2010

Background: Triple negative breast cancer (TNBC) accounts for 15 to 20% of breast cancers. Despite initial chemosensitivity, patients with TNBC had a poor outcome with worse disease-free and overall survivals than others with non-triple-negative breast cancer. The aim of this single-center study was to describe clinical characteristics, pathologic complete response rate, disease-free survival and overall survival rates after neoadjuvant chemotherapy in TNBC.Methods: Forty six consecutive patients with TNBC were treated with neoadjuvant chemotherapy at Georges-François Leclerc Cancer Center. Median follow-up lasted 6.3 years [4.4-10.5y]. Descriptive statistics were performed in this population. Survival rates were calculated according to Kaplan-Meier.Results: Clinical characteristics of patients were the followings: median age was 46 years [24-80y]; 24% had a breast neoplastic hereditary. Initial characteristics of tumors were: 4 T1 (9%), 25 T2 (54%), 17 T3 (37%), 18 N0 (39%), 25 N1 (54%), 3 N2 (7%); 12 grades II (26%), 31 grades III (68%) and 3 (6%) unknown. All the tumors were invasive ductal carcinomas. After neoadjuvant chemotherapy, tumors were classified as pT0 (33%), pT1 (35%), pT2 (30%), pT3 (2%), pN0 (67%) and pN+ (33%). Forty patients (87%) were treated with anthracyclines-based neoadjuvant therapy, 4 (9%) with taxanes and 2 (4%) with another regimen. Pathologic complete response rate was 28.2% according to Chevallier's classification. Forty-five patients (98%) had adjuvant radiotherapy and 20 (43%) had adjuvant chemotherapy. Median disease-free survival was 9.7years [4.4-ND]. The disease-free survival rate was 82.4% [66.6%-91.2%] and 44.8% [23.7%-64%] at 2 and 10 years respectively. Median overall survival was 10.2years [6.4-ND]. The overall survival rate was 97.4% [86.2%-99.6%] and 53.7% [31.8%-71.5%] at 2 and 10 years respectively.Conclusion: The pathologic complete response rate is consistent with that reported in other studies involving neoadjuvant chemotherapy of TNBC and higher than that observed in the other subgroups of breast cancer. However, disease-free and overall survivals are lower than in non triple-negative breast cancers, thereby confirming the worse prognosis of TNBC

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1103.
Estrogen Receptor Expression: Possible Predictor of Pathological Complete Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer Patients.
Authors: Wu J. , Shen K. , Chen X. , Chen C. , Hu Z. , Liu G. , Di G. , Lu J. , Wu J. , Shao Z. , Shen Z.
Published: December 2010

BackgroundEstrogen receptor(ER) status has been found to correlate inversely to pathologic complete response (pCR) rates of neoadjuvant chemotherapy(NAC) of breast cancer. However, not all ER-positive breast cancer respond equally to NAC. The present study aimed to determine the relationship between different ER expression level with pCR in locally advanced breast cancer(LABC) patients who have received NAC.MethodsA retrospective study of 332 female unilateral LABC patients undergoing NAC was performed. All patients were confirmed as invasive breast cancer before treated with NAC, including VE (vinorelbine, epirubicin), CEF (cyclophosphamide, epirubicin, fluorouracil) and PCb regimen (paclitaxel, carboplatin). All patients underwent radical surgery and pCR was defined as the absence of invasive breast cancer in both breast and axillary lymph nodes. ER status were checked using the established immunohistochemical(IHC) method and defined as negative, weakly positive(1+), medium positive(2+) and strongly positive(3+). Binary logistic regression was performed to determine the independent predictors of pCR.ResultsER negativity, 1+, 2+ and 3+ were found in 156, 108, 37 and 31 patients, of which 42(26.9%), 21(19.4%), 3(8.1%) and 1 patients(3.2%) have achieved pCR. Binary logistic regression showed that different ER expression level(P=0.021) and HER2 status(P=0.007, hazard ratio[HR] =2.557, 95% confidence interval[CI]: 1.297∼5.038) were significantly associated with the pCR rates. pCR was much more likely to occur in patients with ER-negative(P=0.024, HR =13.119, 95% CI: 1.402∼122.774) or ER 1+(P=0.025, HR=12.928, 95% CI: 1.388∼120.390) tumors than those with ER 3+ tumors.ConclusionER weekly positive patients also gain considerable benefit from NAC, which is probably less effective in ER strongly positive patients in terms of pCR.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1104.
Sequential FEC 100-Docetaxel (T) Neoadjuvant Chemotherapy (NCT) in Stage II-III Operable Breast Cancer.
Authors: Dubray P. , Dubray P. , Abrial C. , Abrial C. , Mouret-Reynier M. , Mouret-Reynier M. , Nayl B. , Nayl B. , Thivat E. , Thivat E. , Gimbergues P. , Achard J. , Penault-Llorca F. , Penault-Llorca F. , Chollet P. , Chollet P. , Chollet P. , Chollet P. , Durando X. , Durando X. , Durando X.
Published: December 2010

Background: NCT is increasingly used for operable breast cancer to allow breast conservation. Our objective was to evaluate clinical and pathological response after sequential NCT of 3 cycles of FEC 100- 3 cycles of T. This chemotherapy is currently the reference in the adjuvant setting in France.In PACS 01 trial (Roche et al. J Clin Oncol, 2006) FEC followed by T significantly improved 5 years overall survival rates (90.7%) compared to 6 FEC 100 in node-positive breast cancer. However this active combination has not yet been evaluated in NCT.Methods: 101 patients (pts) from February 2005 to September 2008 with pathologically confirmed stage II-III untreated operable breast cancer received 3 cycles (c) of FEC 100 (epirubicin 100 mg/m² + 5-fluorouracil and cyclophosphamide 500mg/m²) followed by 3 c of T (100mg/m²) every 3 weeks. pCR was defined according to Chevallier's (Am J Clin Oncol, 1993) as level 1 and 2 and to Sataloff's classification (J Am Coll Surg, 1995) as grade A. A clinical, mammography and ultrasound breast evaluation was performed at baseline, after 3 c and before surgery.Results: Median age was 52.3 years [28-72]. Median diameter of the tumor was 42 mm [14-100]. 83 pts had a ductal, 14 a lobular, 3 ductal and lobular, 1 another carcinoma. 8.9% were grade I SBR, 58.4% grade II SBR, 28.7% grade III SBR and 4% unspecified. 74 (73.3%) tumors were HR+, 9(8.9%) Her-2 + and 18(17.8%) triple negative. 55 pts (54.4%) were premenopausal.After 3 cycles of FEC 100, ultrasound objective response rate (ORR) was 15%: 13 pts had a partial response and 2 pts had a complete response.After 6 cycles of NCT, ultrasound ORR was 62.5%: 53 pts had a partial response and 7 pts had a complete response.Most frequent grade (G) 3-4 adverse events were neutropenia which occured in 16 pts (15.8%) with G 3 febrile neutropenia in 11 pts (10.9%) (G-CSF optional). Most frequent G 1-2 averse events were nausea which occured in 43 pts(42.6%), myalgia in 27 pts(26.7%) and stomatitis in 23 pts(22.8%).After the completion of NCT, 76 pts (75.2%) underwent breast-conserving surgery. 12(11.9%) achieved pCR using Chevallier's classification and 15(14.8%) using Sataloff's classification.Conclusion: Sequential NCT with FEC followed by T was active and relatively well tolerated. Breast-conserving rate appeared satisfactory.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1105.