bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive factors of resistance to trastuzumab as neoadjuvant therapy in women with HER2-positive breast cancer.
Authors: Jinno Hiromitsu , Sato Tomomi , Takahashi Maiko , Hayashida Tetsu , Hirose Shigemichi , Kitagawa Yuko 
Published: February 2017

168 Background: Despite clinical usefulness of trastuzumab, intrinsic or acquired resistance to trastuzumab is a common clinical phenomenon. However, the mechanisms of resistance to trastuzumab have not been fully elucidated. The objective of this study was to determine the possible mechanisms of resistance to trastuzumab as neoadjuvant therapy in women with HER2-overexpressing operable breast cancer. Methods: Patients with operable breast cancer received 12 cycles of weekly paclitaxel plus weekly trastuzumab before surgery. All tumors were HER2-positive by immunohistochemistry (IHC) or fluorescence in situ hybridization. Expressions of ER, PgR, Ki67, PTEN, phosphorylated IGF-1R (pIGF-1R) and MUC4 were performed by IHC in core needle biopsy samples at baseline. PIK3CA mutation status was evaluated by sequencing of PIK3CA exons 9 and 20 using PCR amplification and direct sequencing. Results: Thirty-seven patients were enrolled and assessable for clinical and pathologic responses. The pCR rate was 48.6% (18/37). Negative, moderate and strong membranous expression of MUC4 was observed in 3 (8.1%), 18 (48.6%) and 12 (32.4%) patients, respectively. Membranous staining for pIGF1-R was negative in 24 (64.9%) patients. PTEN loss was observed in 33.3% (8/24) of the tumor examined. PIK3CA sequence analysis of the 13 tumors identified 2 mutations in exon 20 and 2 mutations in exon 9, corresponding to a PIK3CA mutation frequency of 30.8%. MUC4 status did not affect the pCR rate. Although membranous pIGF1-R expression did not affect pCR rate in hormone receptor-positive patients (66.7% vs. 50.0%), hormone receptor-positive patients with positive membranous pIGF1-R tended to show higher pCR rate compared with negative pIGF1-R (41.2% vs. 0%). PTEN loss and/or PIK3CA mutation were not significantly associated with pCR rate. Conclusions: These data indicate that aberrant downstream signaling caused by loss of PTEN and/or PIK3CA mutation, alternative signaling from IGF-1R and masking with MUC4 were not important mechanisms of resistance to trastuzumab.
Epidemiologic and survival characteristics of breast cancer (BC) among the U.S. Asian Indian and Pakistani women compared with other U.S. population groups: A SEER database study.
Authors: Raza Shahzad , Hossain Akm Mosharraf , Rahman Rubayat , Freter Carl , Abraham Jame 
Published: February 2017

19 Background: The Asian Indian/Pakistani population living in the U.S. (USAIP) is a rapidly growing minority group with persistent cancer disparities. According to SEER (Surveillance, Epidemiology, and End-Result) database, BC is the most frequently diagnosed cancer in USAIP women.The customizing therapeutic and preventive approaches are important to improve health quality across different population therefore, we conducted the largest epidemiological and survival disparities of BC in USAIP women. Methods: SEER has been collecting and reporting data on USAIP as a separate ethnic group since 1988. Using 18 SEER registries from 1988-2009 and SEER*Stat 7.0.9, we performed frequency and survival sessions (Kaplan-Meier adjusted for age) on USAIP women with BC and compared with non-Hispanic White (NHW), Hispanics (H),and African American women (AA) with BC. Cox proportional hazards regression analysis was performed to estimate relative risks (RR) on BC mortality after adjusting confounders using SAS v 9.3. Results: A total of 2,750 BC cases reported in USAIP women in SEER database, accounting (38%) of all cancers compare to NHW (30%), H (31%) and AA (32%). The median age at diagnosis in USAIP is significantly less (54 y, p < 0.001) than other ethnicities. Significantly more USAIP (14%, p < 0.001) were diagnosed at age < 40y vs NHW (5%), H (7%) and AA(10%). Compare to NHW, USAIP were more likely to have stages III or IV (22% vs. 18%, p < 0.01); ER/PR+ (84% vs. 75%, p < 0.001); poorly differentiated histology (47% vs. 35%, p < 0.001). 5 yr overall survival is better in USAIP (97%, p <0.01) vs NHW (87%), H (83%) and AA (75%). RR of death from BC in US AIP was higher with age (> 71y), stage III or IV, high grades, ER/PR negative, divorced/widowed, and diagnosis year (1988-1994). Conclusions:This study identifies unique biological features and disparities of BC in US AIP women compared with other US populations. The difference in survival is intriguing, and could be due to differences in tumor biology, access to care, and other epigenetic factors.This study has potential implications for screening and therapeutic recommendations for BC in the US AIP population.
Does removal of DCIS decrease the incidence of invasive breast cancer?
Authors: Killelea Brigid K. , Christy Carla J. , Horowitz Nina Ruth , Tsangaris Theodore , Dixon Mike , Chagpar Anees B. , Grube Baiba J. , Lannin Donald R. 
Published: February 2017

2 Background: SEER data have shown that as the incidence of high grade DCIS increases, high grade invasive cancer decreases; but this is not true for low-grade DCIS. The purpose of this study was first to determine what proportion of DCIS is calcified, and second to explore the relationship between grade, invasiveness, and calcification, in an effort to model the effect of removing mammographically detected DCIS. Methods: A single-institution, retrospective review was performed to identify all patients diagnosed with DCIS or invasive cancer from 2003-2011 who had corresponding mammograms. Results: There were 337 cases of pure DCIS, 309 cases of pure invasive tumor, and 847 cases of invasive tumor with a DCIS component. Grade 3 invasive cancers were much more likely to be associated with DCIS compared to grade 2 or 1 cancers. (83% vs. 70% vs. 54%, p<0.001). Of the 1,184 cases with DCIS or a DCIS component, 601 (51%) were associated with mammographic calcifications. The presence of calcifications was strongly associated with DCIS extent, comedo and micropapillary histology, presence of necrosis, and grade of DCIS (p<0.001 for each). High grade DCIS was almost twice as likely to be calcified compared to low grade. Extrapolation to SEER data suggests that there is a large reservoir of undetected, non-calcified DCIS and this is largely of low grade. Conclusions: These findings may explain why breast screening has reduced the incidence of high-grade invasive cancers, through diagnosing and excising high-grade DCIS, and yet has failed to reduce the incidence of low-grade cancers. [Table: see text]
Prognostic significance of p53 overexpression in luminal HER2-negative type breast cancer.
Authors: Kikuchi Shoichi 
Published: February 2017

35 Background: In this study, we evaluated the prognostic significance of p53 overexpression, because it was reported that there was a significant correlation between p53 and resistance to endocrine therapy, and prognosis. Methods: A retrospective analysis was performed using 2,332 primary breast cancer patients who underwent surgery between 2001 and 2010. There were 1,899 cases with luminal subtypes (905 cases: HER2-negative and Ki67 low type; 808 cases: HER2-negative and Ki67 high type; and, 186 cases: HER2-positive type), 155 cases with HER2-enriched subtypes, and 278 cases with triple-negative subtypes. Luminal type was defined as ER-positive cell rates ≥ 1%, regardless of PgR status. The cut-off value of the Ki67 index was 20%. Moreover, tumor size, nodal status and nuclear grade were studied in relation to disease free (DFS) and overall survival (OS) using the Cox proportional hazard model. Results: We found that p53 overexpression was present in 10% of the patients and significantly correlated with larger tumors, younger age, positive nodes, a higher grade, negative ER/PgR, a higher Ki67, and positive HER2. The patients with p53 overexpression had significantly unfavorable prognosis, especially in the patients who only received endocrine therapy. There were 26 cases in the luminal HER2 negative and Ki67 low type group that had p53 overexpression and showed a significantly shorter DFS. In the univariate analysis for DFS, p53, Ki67, tumor size, nuclear grade and nodal status were significant factors in luminal HER2 negative type. In the subsequent multivariate analysis for DFS, the p53 status was one of the most significant factors. Conclusions: The p53 overexpression was a significant prognostic factor in luminal type breast cancer. Therefore, the prognostic evaluation of luminal HER2 negative type breast cancer might be improved using an immunopanel, which includes Ki67 and p53. Moreover, it might isolate the patients who are resistant to endocrine therapy.
Presentation and pathology of breast cancer in patients with HIV.
Authors: Rosenblatt Paula , Singh Sukhwant Nikki , Goicochea Lindsay , Kesmodel Susan , Ioffe Olga B. , Chumsri Saranya , Riedel David 
Published: February 2017

39 Background: With the use of highly active antiretroviral therapy, it is postulated the prevalence of breast cancer will increase in the HIV infected population. Few studies have evaluated the presentation and pathological features of breast cancer in this population. Methods: Charts of approximately 5,000 HIV patients seen between 2000-2011 at the University of Maryland were reviewed to identify those diagnosed with breast cancer. Demographics, HIV data, cancer clinical presentation, family history, and pathologic findings were collected. Pathologic findings included receptor status (estrogen [ER], progesterone [PR], and human epidermal growth factor 2 [HER2]), grade, stage, lymphovascular invasion (LVI), multifocality/multicentricity (MF/MC), and presence of carcinoma in-situ. Results: Twenty cases of concomitant HIV and breast cancer were identified. At diagnosis of cancer, the median age, CD4 count, and duration of HIV infection were 48 years, 437 cells/mm3, and 6 years, respectively. 47% had a family history of breast or ovarian cancer. 79% self-palpated a mass. Pathologic findings included 18 invasive ductal carcinoma, 1 invasive lobular carcinoma, and 1 ductal carcinoma in-situ. 70% were ER-positive, 50% were PR-positive, and 47% were HER2-positive. 21% were Grade 1, 21% were Grade 2, and 57% were Grade 3. 21% luminal A (ER/PR+, HER2- and Ki67 ≤14%), 52% luminal B (ER/PR+, HER2+ or Ki67>14% or grade 3), 5% HER2 enriched (ER/PR-, HER2+), and 21% triple-negative/basal (ER/PR-, HER2-). 5% were stage 0, 40% were Stage I, 30% were Stage II, 25% were Stage III, and none were Stage IV. LVI was present in 36%, MF/MC was present in 35%, and carcinoma in-situ was present in 82%. Conclusions: Compared to historical data of non-HIV infected individuals, our population presented at a younger age with a strong family history and a greater number of self-palpated breast masses. HIV-infected patients with breast cancer presented with more HER2 positivity, higher grade, less favorable luminal B subtype, and more MF/MC disease. Despite aggressive pathology, most patients still presented with a relatively early stage. Annual screening mammogram at earlier ages should be considered in HIV-infected patients, particularly in patients with positive family history.
Pre-morbid anthropometric measurement and its impact on outcome in early-stage breast cancer in midwestern Ireland.
Authors: Quintyne Keith Ian , Woulfe Bernie , Gupta Rajnish K. 
Published: February 2017

45 Background: Obesity has become a grave public health concern of global proportions, especially in many developed counties. Clinical obesity may be defined as a body mass indeed (BMI) of greater than or equal to 30kg/m2. Within recent times, growing interest has been seen for the relationship between obesity and cancer; with it being identified as a significant risk factor. It has also been appreciated that it is one of the greatest modifiable risk factors for malignancy. Obesity at the time of diagnosis of early-stage breast cancer (EBC) has been associated with poor outcome, especially breast-cancer specific survival. The potential mechanism for this has been linked to several factors including: associated adverse disease features; hormonal influences; co-morbidities that can interfere with therapy; and other yet unknown pathways. We herein report our experience on patients with newly diagnosed EBC and related pre-morbid anthropometric data and its impact on their outcome in an ambulatory Medical Oncology practice in Mid-Western Ireland. Methods: Study period: 01/01/2001 – 31/12/2010. Retrospective data was derived from (1) MWCC Oncology database, (2) pathology reports, and (3) patient files. Data was collated and entered into an Access database and exported into IBM SPSS Statistics 20 version for statistical analysis. Results: One thousand and forty-one (1,041) patients with EBC were identified and analysed. Median age: 55 years (23 – 87 years). Median follow-up: 5.04 years. BMI distribution revealed: Underweight (<18.5kg/m2): 1%; Normal (18.5 – 25kg/m2): 33%; Overweight (25.1 – 30kg/m2): 39%; and Obese (>30kg/m2): 27%. It was noted that obese patients had disproportionately later age of presentation, larger tumours, ductal carcinoma on histology and a smoking history (including current and former smokers). Obese patients accounted for 50% of the non-cancer related deaths observed. Obese patients showed poorer survival in all categories, but it was only statistically significant for non-cancer related deaths. Conclusions: Pre-morbid anthropometric data has shown that obese patients had poorer outcome, and highlights that potential intervention can have impact on improving outcome in EBC.
Predictors of regional recurrences in breast cancer patients with negative sentinel node.
Authors: Matsumoto Akiko , Takahashi Maiko , Hayashida Tetsu , Jinno Hiromitsu , Kitagawa Yuko 
Published: February 2017

51 Background: For patients with clinically node-negative, early-stage breast cancer, sentinel lymph node biopsy (SLNB) has replaced axillary lymph node dissection (ALND) as a standard method for staging of regional lymph nodes. Regional recurrences after negative (SLNB) have generally been reported in the range of 0.5 to 2% and factors associated with regional recurrence in patients with negative SLNB are still to be elucidated. In this study, we evaluated regional recurrence rates and predictors of regional recurrences in patients with negative SLNB. Methods: Between January 2001 and December 2012, 1,322 patients with clinical node-negative invasive breast cancer less than 3cm underwent SLNB at Keio University Hospital. Of 1,322 patients with SLNB, 1,033 patients with negative SLNs were included in this study. Sentinel lymph nodes (SLNs) were detected using a combined method of blue dye and small-sized technetium-99m-labeled tin colloid. Intraoperative frozen examination was performed with hematoxylin and eosin (HE) staining. SLNs, fixed and embedded in paraffin, were additionally diagnosed with HE staining and immunohistochemical analysis. Results: Median age was 57.0 years (range, 25-89) and median tumor size was 1.9cm (range, 0.5-6.0cm). After a median follow-up of 54.8 months, there were 13 regional (1.3%) and 26 distant recurrences (2.5%). Median disease-free interval of regional and distant recurrences was 32.6 and 22.7 months, respectively (p=0.761). Higher nuclear grade (NG) was significantly correlated with regional and distant recurrences (p=0.001 and p=0.008). The rate of lymphovascular invasion (LVI) was significantly higher in patients with regional recurrences comparing with patients without recurrences (58.3% vs. 27.6%, p=0.026), however LVI was not a significant predictor of distant recurrences (p=0.072). Estrogen receptor negativity was significantly correlated with distant recurrences (p=0.013), whereas it was not associated with regional recurrences (p=0.626). Conclusions: Regional recurrences were rare in early-stage breast cancer patients with negative SLNB. LVI and NG can be used as predictive factors of regional recurrences after negative SLNB.
Sentinel node biopsy after neoadjuvant therapy: Relevance of sentinel node micrometastases, isolated tumor cells, and value of immunohistochemistry.
Authors: Boileau Jean-Francois , Poirier Brigitte , Basik Mark , Holloway Claire , Gaboury Louis , Sideris Lucas , Meterissian Sarkis H. , Arnaout Angel , Brackstone Muriel , McCready David R. , Karp Stephen Eric , Wright Frances Catriona , Younan Rami , Provencher Louise , Patocskai Erika , Omeroglu Atilla , Robidoux Andre 
Published: February 2017

52 Background: Sentinel node biopsy (SNB) is used in breast cancer patients that present with clinically negative nodes. In this setting, most guidelines do not support the use of immunohistochemistry (IHC) and recommend against completion node dissection (CND) when only isolated tumor cells (pN0(i+)) or micrometasases (pN1mi) are identified. When SNB is used after neoadjuvant therapy (NAT), the relevance of ypN0(i+) and ypN1mi sentinel nodes (SNs) and the value of IHC are not well established. The goals of this study are to determine if CND should be recommended in the presence of ypN0(i+) or ypN1mi SNs and if IHC should be used to evaluate SNs after NAT. Methods: From March 2009 to December 2012, 152 women with biopsy proven node positive breast cancer were accrued to the multicentric prospective SN FNAC trial. After NAT, SNB was followed by a CND in all participants. SNs were cut in serial slices no thicker than 2 mm. Hematoxylin and eosin stains (H and E) were done on all slices, and if negative, IHC was used. The size of the largest SN metastasis and the primary method of identification (H and E or IHC) were recorded. ypN0(i+), ypN1mi and ypN1 SNs were considered as positive. Pathology was centrally reviewed. Results: 145 women were eligible for the trial. Axillary pathologic complete response rate = 34% (49/145). SNB success rate = 88% (127/145). False negative rate = 8.4% (7/83). If ypN0(i+) SNs are classified as node negative, the false negative rate is increased to 13.3% (11/83). For patients with ypN0(i+) (n=7), ypN1mi (n=8) and ypN1 (n=61) SNs, the rates of non-SN involvement are 57%, 38% and 56% respectively (p=NS). 40% (27/68) of positive SNBs are primarily detected by IHC. This is increased to 64% (9/14) for the identification of SN metastases ≤ 2mm. Conclusions: After NAT, particularly when presenting with biopsy proven node positive breast cancer, patients with ypN0(i+) and ypN1mi SNs have a significant rate of non-SN involvement. In the absence of evidence to show that a CND can be safely avoided, efforts should be made to identify even minimal amounts of disease when SNBs are done following NAT. IHC is useful to increase the detection of small SN metastases in this setting. Clinical trial information: NCT00909441.
Association of MRI and locoregional recurrence (LRR) rates in ductal carcinoma in situ (DCIS) patients treated with or without radiation therapy (RT).
Authors: Pilewskie Melissa Louise , Olcese Cristina , Eaton Anne , Patil Sujata , Morris Elizabeth Ann , Morrow Monica , Van Zee Kimberly J. 
Published: February 2017

57 Background: Perioperative MRI is frequently obtained in women with breast cancer; however, studies have not shown decreased rates of re-excision, and some report unnecessary increases in mastectomy rates. We examined LRR rates among women with DCIS who underwent perioperative MRI as compared to those who did not. Methods: All women who underwent breast-conserving surgery for DCIS in 1997-2010 were included from a prospectively maintained database. Patient characteristics and rates of LRR were compared in women with and without an MRI. Univariate and multivariate analyses were performed. Analysis was repeated in the subset of women who did not receive RT. Results: 2,321 cases were identified; 596 had MRI and 1,725 did not. Women who had MRI were younger, more likely to be premenopausal, have a family history of breast cancer, have a clinical presentation, receive RT and endocrine therapy, be treated in later years, and had fewer close/positive margins. At median follow-up of 57 months there were 184 IBTRs; 5-year LRR rates were 8.5% (MRI) and 7.2% (no MRI) (p = 0.52), and 8-year rates were 14.6% and 10.2%, respectively. MRI was not associated with lower LRR rates after adjustment for age, menopausal status, family history, presentation, adjuvant therapy, margin status, number of excisions, and year of surgery in both the entire cohort and in the subgroup who did not receive RT. Select factors from multivariate analysis for patients with all covariates available are shown in the Table. Conclusions: We observed no association between perioperative MRI and LRR rates for patients with DCIS, even when RT was not given. The benefit of perioperative MRI for DCIS remains uncertain. [Table: see text]
The impact of recurrence score (RS) performed on pretreatment (Tx) core biopsies (CB) in predicting response to neoadjuvant chemotherapy (NCT) in patients (Pts) with ER+ breast cancer (BC).
Authors: Soran Atilla , McGuire Kandace P. , Ahrendt Gretchen , Bonaventura Marguerite , McAuliffe Priscilla F. , Diego Emilia , Serrano Merida , Johnson Ronald 
Published: February 2017

63 Background: The Oncotype DX 21-gene assay is beneficial in predicting disease-free survival and local regional relapse in hormone receptor BC. The ability of the assay to predict response of primary BC to NCT is less well studied. We hypothesize a (+) association exists between the RS result on pre-Tx CB and % tumor response (%TR) after NCT on final pathology. Methods: Pre-Tx RS was measured on paraffin-embedded CB from 60 pts with ER+ Her2(-) BC who then received NCT and for whom post-Tx pathology was available. %TR is calculated as 100 x (pre-Tx size – post-Tx size)/pre-Tx size. Pre-Tx tumor size was determined using imaging measurements selected in the following preferential order: MRI, US or mammogram. Post-Tx tumor size was calculated as the product of: maximum dimension of tumor-bed/fibrosis and % change in cellularity (compared with pre-therapy biopsy). Partial response (PR) is defined as ≥50% reduction in TR. Results: Mean pre-Tx tumor sizewas 4.8 (range 1-23) cm. 83% of pts were clinically lymph node (-). Nottingham Score was >6 in 93%. Breast conserving surgery was performed in 17 (28%) pts. Median RS was 20 (range 3-69). Median %TR was 42 (range 0-97)%. There were no pCRs. PR was observed in 43% of pts. No association was found between %TR and pre-NCT tumor size, age, Nottingham score or node status (p>0.05). No association for the RS as a continuous or categorical variable with %TR (p>0.05) was seen. There is a non-significant (p=0.07) trend toward increased response to NCT with increasing RS. Response to NCT improved as values of ER (p=0.02) and HER2 (p=0.007), by RT-PCR as reported with the RS, decreased. Conclusions: In the subset of patients with ER+ BC, where NCT was recommended to affect tumor downstaging, RS did not successfully discriminate pts that would respond to NCT as measured by %TR. While there was a trend toward better response with higher scores, the result was nonsignificant. The use of this genetic assay to discriminate between NCT and hormonal therapy requires further study. [Table: see text]