bluuebunny/crossref_metadata_2025 huggingface dataset:
Neoadjuvant therapy and rates of margin re-excision in patients with invasive breast cancer.
Authors: Hanna E. M. , Musunuru S. , Flippo-Morton T. , Sarantou T. , Norton H. J. , Calhoun M. , White R. L.
Published: February 2017

131

Background: Many patients with invasive breast cancer receive neoadjuvant chemotherapy (NACT) prior to undergoing definitive surgical management in an effort to facilitate breast conservation. This study compares the re-excision rates of patients undergoing NACT with those who proceed directly to surgical treatment. A retrospective review of all breast cancer patients treated with neoadjuvant chemotherapy between November 2007 and June 2010 was performed. Re-excision rates were calculated for patients who received NACT and were then compared to a group of contemporaneous patients who did not receive neoadjuvant treatment (non-NACT). Re-excisions were routinely performed for disease <2mm from the margin. Patients with DCIS or LCIS were excluded. For statistical analysis, t-test and chi square tests were performed using SAS v9.2.

Results: During the study period, 152 patients received neoadjuvant chemotherapy and then underwent surgical treatment of breast cancer. Of these patients, 108 (71.0%) underwent partial mastectomy as primary treatment, 44 (29.0%) underwent mastectomy. As a comparison group, we evaluated 188 consecutive patients diagnosed with invasive breast cancer who underwent initial treatment in the form of partial mastectomy. Table 1 demonstrates the characteristics of NACT and non-NACT patients and margin re-excision rates.

Conclusions: Neoadjuvant chemotherapy is often administered in an effort to allow women with larger tumors to pursue breast conservation therapy. This study demonstrates that the rate of margin re-excision in NACT patients is not statistically different from those patients who undergo partial mastectomy as their primary treatment.

[Table: see text]
Neoadjuvant endocrine therapy with exemestane in locally advanced breast cancer: The initial results from a Brazilian breast cancer center.
Authors: Marziona F. , Mattar A. , Hegg R. , Belloni S. J. , Rocha S. B. , Tavares E. G. , Monteiro W. M. , Carneiro A. Q. , Kuwamoto S. M. , Gebrim L. H.
Published: February 2017

135

Background: Endocrine therapy is a well-established treatment for hormone-positive breast cancer, both in the adjuvant and the metastatic setting. Neoadjuvant chemotherapy has been used to increase the number of patients who are eligible for breast-conservation therapy (BCT) by inducing tumor downstaging. Neoadjuvant endocrine therapy (NET) is mostly used in patients who are not eligible for chemotherapy (almost reserved to postmenopausal patients). The clinical response with NET in postmenopausal patients with locally advanced breast cancer (LABC) and positive hormonal receptors is almost 75% with aromatase inhibitors (AI). The comparison among tamoxifen and the three AI (anastrozole, letrozole, and exemestane) shows a superiority to AI regarding BCT. There are few data in premenopausal women and NET.

Methods: 29 women with rich positive hormone receptor were enrolled in the study between January to September of 2010. Patients received exemestane 25mg/day (EXE) and as we included both pre (12 patients) and postmenopausal (17 patients) women, the premenopausal ones were submitted to ooforectomy.

Results: All patients were clinical stage III. In the premenopausal group 6 patients were submitted to surgery and 5 are still taking EXE. Between the two groups 9 patients were submitted to surgery, 4 showed response and are scheduling to surgery, 10 are still taking exemestane. Five patients had serious comorbidities and were submitted to radiotherapy after 9 months of EXE (one without clinical tumor) and are asymptomatic for at least 4 months. Just one patient (premenopausal) had tumor progression after 5 months of EXE and was switched to chemotherapy. Most common side effects were arthralgia/myalgia grade 1/2.

Conclusions: In Brazil LABC is frequent and neoadjuvant chemotherapy is the standard treatment. We offered a treatment with a lower cost and especially lower side effects. Because of the initial stage, BCS was not possible, but we had clinical response in about 75% of the patients. This approach was good for patients with comorbidities, and despite the NET is not established for premenopausal patients our initial results encourage us to recommend it.
CYP2D6 and ESR genotypes in adjuvant tamoxifen treatment for early breast cancer.
Authors: Kim K. , Jung K. H. , Ahn J. , Kim S. , Kim H. J. , Ko B. , Lee J. W. , Son B. H. , Ahn S. , Gong G.
Published: February 2017

142

Background: The pharmacokinetics and pharmacodynamics of tamoxifen may influence the clinical outcome and tolerability of adjuvant treatment with tamoxifen in breast cancer. We investigated the effects of polymorphisms of CYP2D6, ESR1, and ESR2 for tamoxifen therapy in early stage breast cancer patients.

Methods: Tissue DNA from 187 patients who received tamoxifen only as an adjuvant systemic therapy between 1997 and 2002 were extracted and genotyped for polymorphisms of CYP2D6 (*2A, *10, *14, *41) and estrogen receptor (ESR1, ESR2). While CYP2D6*10, *14 and *41 have been reported to be associated with decreased activation of tamoxifen, CYP2D6*2A, ESR1 PvuII CC and ESR2-02 GG have been associated with enhanced activity of tamoxifen. Statistical analyses include Fisher exact test, Chi-square and Kaplan-Meier analyses.

Results: Median age was 43 years (range 25-49). Most of the patients (170/187) were stage I, while other patients were stage 0 (1/187) and stage II (17/187). None of the patients had nodal metastasis. Median follow-up was 100 months (7-166). Allele frequencies were as follows: CYP2D6*10, 0.69; *14, 0.02; *41, 0.01; *2A, 0.64; ESR1 PvuII C allele, 0.25; ESR2-02 G allele, 0.98. Each genotype group did not show significant differences in age, stage, pT, tumor size and follow up period. Twelve percent (24/187) had received tamoxifen therapy for less than 24 months. Of the 24 patients, 67% (16) discontinued tamoxifen therapy related to tolerability issues. Recurrence occurred in 12 patients (6.4%). There was no association between genotypes with either recurrence or tamoxifen duration < 2 years. Although statistically nonsignificant, patients with either CYP2D6*2A homozygote, ESR1 PvuII CC genotype, ESR2-02 GG genotype tended to have a longer DFS when compared concomitantly to wild-type (p=0.445).

Conclusions: Polymorphsims for CYP2D6*2A,*10, *14, *41, ESR1 PvuII, ESR2-02 did not show significant associations with either recurrence or tamoxifen duration > 2 years. However, grouped analysis for CYP2D6*2A, ESR1 PvuII, ESR2-0210 genotypes need further evaluation regarding with tamoxifen outcome.
Relationship of recent pregnancy and cytologic atypia in the contralateral breast of patients with breast cancer.
Authors: Revesz E. , Zalles C. M. , Ivancic D. , Bethke K. P. , Hansen N. M. , Jeruss J. S. , Khan S. A.
Published: February 2017

149

Background: Although early parity protects against breast cancer later in life, it is a risk factor in the years following pregnancy, particularly when child-bearing is delayed. In a separate study, we have reported that these pregnancy-associated breast cancers (PABC) are more likely to be hormone receptor (HR) negative; we have previously found that random fine needle aspiration (rFNA) of the contralateral breast (CB) frequently have atypia in women with HR negative breast cancer. We now report an analysis of the cytological features of contralateral rFNA in relation to recent parity, with the goal of assessing cytological features which may be risk factors for PABC.

Methods: Women with breast cancer undergoing surgery between 2006 and 2008 were enrolled in a prospective study of rFNA of the CB. Cytological analysis was performed on all the samples, using two scoring systems, Masood and Zalles (M and Z). Linear regression analyses were performed relating each score to interval from last pregnancy, stratified for parity, and adjusted for age.

Results: Eighty-two patients had rFNA and cytologic analysis. The parous group’s (n=52) interval since last pregnancy was inversely correlated with the overall M score (p=0.034); pleomorphism and (p=0.047 and p=0.013 respectively). M score was also related to age at last pregnancy (p=0.026) as were pleomorphism and chromatin pattern (p=0.044 and 0.035 respectively). In the nulliparous group (n=30), there were no significant relationships between any of the cytological parameters or age.

Conclusions: The CB of women with recent parity display specific cytological abnormalities that are related to risk of breast cancer, particularly HR negative breast cancer. This observation affords the opportunity to further evaluate rFNA as a tool for breast cancer risk assessment following pregnancy, and to identify molecular correlates of nuclear cytological abnormalities that may serve as targets for prevention of ER negative breast cancer.
An international perspective: The role of nurse involvement in improving breast cancer control.
Authors: Blauvelt B. M. , Podder S. K. , Abulkhair O. , Barrios C. H. , Huang C. , Kim S. , Shockney L. D.
Published: February 2017

152

Background: Non-Western, non-Caucasian populations comprise 90% of the world’s estimated 3.2 billion women, living mostly in low and middle income nations. While medical advances have greatly reduced breast cancer morbidity and mortality in developed nations, those are on the rise in many low and middle income nations. The purpose of the study was to identify emerging needs and challenges observed by breast cancer thought leaders in diverse regions of the world consisting mainly of lesser developed nations to identify strategies for improving breast cancer control.

Methods: 225 breast cancer medical, advocacy and policy leaders from 30 countries in Latin America, Asia, the Middle East/North and South Africa, Canada and Australia participated in this study. The study sample was composed of 203 breast cancer specialists, 12 patient advocates and 10 policy makers.

Results: The most salient needs and challenges identified were to: (1) develop nurses trained in breast cancer patient and family care, management, education and clinical research (48%); (2) individualize breast cancer therapy (47%); and (3) improve understanding of the reasons for apparently higher proportions of younger women presenting with more aggressive tumors among these predominantly non-Caucasian populations (45%). Analysis of these and other needs identified evolved into 4 key themes and sub-dimensions involving nurses to improve breast cancer control: Capacity, Research, Advocacy and Access.

Conclusions: The most significant need identified by this study was to increase both the capacity and capability of breast cancer nurses. A comprehensive approach to doing this would include: (1) increasing capacity to educate nurses in breast cancer patient education and related care issues in nursing schools and teaching hospitals; (2) working with local medical societies, educational institutions and governmental authorities to enable nurses to work as primary care practitioners; and (3) increasing participation of nurses in breast cancer clinical research, working with clinicians and in collaboration with breast cancer research centers of excellence from around the world.
The impact of ethnicity and insurance status on stage of cancer at diagnosis and overall survival of breast cancer.
Authors: Omaira M. , Mozayen M. , Mushtaq R. , Katato K.
Published: February 2017

154

Background: Major advances in early diagnosis and treatment of breast cancer (BC) have been achieved with significant declines in mortality. However, not all segments of the United States population have experienced equal benefits from this progress. Though ethnic disparities in BC outcome have been attributed to lack of adequate health insurance, the differences in outcome when insurance and socioeconomic status are similar still exist. We elected to examine the effect of insurance status at diagnosis, and whether race is an independent risk of poor outcome in a population from a community-based cancer database.

Methods: A retrospective study on BC among patients aged 18 to 64 years were identified, between 1993 and 2005, using data from the Tumor Registry at Hurley Medical Center in Flint, Michigan. Patient’s characteristics included age, race, stage at diagnosis, and primary payer. Insurance status was classified as uninsured/Medicaid, private insurance, and Medicare disability (Medicare under age 65). The 5-year overall survival (OS) was calculated, in respect to patient ethnicity, and compared between the three insurance groups using Fisher’s exact test.

Results: A total of 779 patients have been identified with diagnosis of BC. 147 patients were excluded due to incomplete data. 632 patients were analyzed. African Americans were 228 (36%), Caucasians 391 (62%), and other ethnicities 13 (2%). Mean age at diagnosis was (49.21) for African Americans versus (51.35) for Caucasians (p = 0.002). African Americans were more likely to present at advanced stage (III, IV) than Caucasians (17% versus 10%, p = 0.017). However, this difference was not statistically significant when adjusting for insurance status. Although both ethnicities had similar OS in respect of their insurance group, patients with Medicaid/uninsured had significantly lower OS compared to patients with Medicare disability (p = 0.006) and private insurance (p < 0.0001) respectively.

Conclusions: Uninsured/Medicaid patients with breast cancer have worse outcome when compared to patients with Medicare or private insurance. Ethnicity is not an independent risk factor of advanced stage at diagnosis and poorer outcome.
Relationship between differences in RNA or protein expression and the effects of race/ethnicity on breast cancer outcomes.
Authors: Chavez-MacGregor M. , Liu S. , Chen H. , Do K. , Pusztai L. , Symmans W. F. , Hortobagyi G. N. , Mills G. B. , Meric-Bernstam F. , Gonzalez-Angulo A. M.
Published: February 2017

157

Background: Race is associated with distinct outcomes for breast cancer patients. The purpose of this study was to evaluate whether there were differences in gene or protein expression patterns between breast cancers according to race/ethnicity and cancer subtype [(triple-negative (TN), estrogen receptor-positive/HER2-negative (HR+) and HER2-positive/with any ER status (HER2+)].

Methods: Fine needle aspirates from primary breast cancers were obtained under a prospective tissue collection protocol. Transcriptional profiling was performed using Affymetrix HG-U133A platform in 376 patients and reverse phase protein array analysis (RPPA) was done for 177 distinct proteins in 255 patients from a separate cohort. Unsupervised clustering was conducted, as well as supervised comparison by race and tumor subtype. BRB-Array tools and Ingenuity Pathways software packages were used to analyze the data.

Results: Median age was 50 years in both cohorts. In the RPPA cohort 54.5% of the tumors were HR+, 20.7% HER2+ and 24.71% TN. One hundred and forty-seven (57.6%), 47 (18.43%), 46 (18.1%) of the patients were white, Hispanic, and black, respectively. Unsupervised hierarchal clustering of the protein expression data showed no distinct clusters by race (permutation p values were 0.492, 0.489 and 0.494 for the HR+, HER2+ and TN tumors respectively). In the gene expression cohort, 54.2% of the tumors were HR+, 16.5% HER2+ and 29.3% TN. Two hundred and sixteen (57.5%), 111 (29.52%), and 32 (8.52%) patients were white, Hispanic and black, respectively. No probe set with an FDR < 0.05 showed any association with race by breast cancer subtype; similar results were obtained using pathway and gene set enrichment analysis methods.

Conclusions: These results indicate that there are no large scale gene and protein expression differences between breast cancers of different races. The study size is too small to confidently exclude small scale expression differences in a limited number of proteins or RNAs. This analysis also did not examine the potential differential distribution of DNA nucleic acid polymorphisms, somatic mutations, gene rearrangements or copy number aberrations by race-ethnicity.
Predictions for positive nodes in breast cancer using computerized modeling.
Authors: Gawlick U. , Hewitt K. , Tamayo P. , Mone M. C. , Hansen H. J. , Nelson E. W.
Published: February 2017

16

Background: The accuracy and consistency of sentinel lymph node (SLN) biopsy for axillary staging in breast cancer has been well established by multiple studies. Although the standard of care has been to perform a completion axillary lymph node dissection (ALND) on patients who have a positive sentinel node, recent data (ACOSG Z0010, Z0011 and NSABP B-32) suggests that an ALND may be avoided in certain subsets of patients. To further study this question, we used a Bayesian model to predict the probability of finding disease in the ALND for breast cancer.

Methods: All SLN procedures performed by a single surgeon, for clinical T1-T2 N0 disease between September 2000 and March 2009 were retrospectively reviewed under an IRB approved protocol. Demographic, disease and surgical procedural variables were collected. Values are reported as mean ± standard deviation. A Bayesian model, a standard statistical model frequently used in medicine, was used to identify variables that could predict a positive ALND.

Results: A total number of 235 SLN procedures were reviewed. The mean patient age was 58.6 ± 11.8 (range 28-88), tumor size was 1.8 ± 1.3 cm (range 0.2-7.4), and BMI was 28 ± 6.1. The number of SLN found was 3.6 ± 1.9 (range 0-10), and in 2 cases no SLN were found, for an overall failure rate of 0.85%. A total of 73 ALND were performed in this group; 27 cases had ALND as national study participants randomized to ALND, 44 cases for positive SLN, and 2 cases in which no SLN could be identified. The mean number of axillary lymph nodes removed was 14.8 ± 7 and the mean number of positive axillary nodes was 2.7 ± 4.1. Tumor size, tumor grade, number of positive SLN by hematoxylin and eosin staining, and a low technetium count of the first SLN were found to be significant predictors of positive axillary nodes during a completion ALND. There was also a trend for progesterone receptor expression as a predictor of axillary disease.

Conclusions: A model to predict a positive ALND for breast cancer is presented. We found tumor characteristics, number of positive SLN and low technetium count for first SLN to be predictors for finding axillary disease. Further studies are needed to validate our model as a means of sparing women an ALND who have a low probability of finding additional breast disease.
Use of a meal replacement weight loss intervention in survivors of ER/PR-negative breast cancer.
Authors: Milliron B. , Hopkins J. O. , Fulmer A. , Case L. D. , Vitolins M.
Published: February 2017

166

Background: The detrimental relationship between body mass index and recurrence has been more pronounced among women with estrogen receptor/progesterone receptor (ER/PR)-negative breast cancer. Although studies have reported that soy-based meal replacements can favorably impact weight and other metabolic risk factors, meal replacement strategies have not been tested in this population. The objectives of this pilot study were to determine the feasibility of a soy-based meal replacement intervention, to measure changes in anthropometrics and biomarkers, and to measure changes in health-related quality of life (QOL).

Methods: The 3-month intervention included education sessions, meal replacement products, meal plans, and physical activity promotion. Anthropometrics, blood samples, and questionnaire data were collected. Paired t-tests assessed changes over time in continuous measures. Weights were measured weekly and a mixed model regression analysis assessed change in weight over time.

Results: Nineteen women participated in the study (mean age 59 years). When comparing pre and post intervention weights, women lost ~7.5 ± 4.9 kg (p < 0.001) and had significant improvements in health-related QOL. Women lost 7.5% of their baseline weight which exceeded our study goal (5% reduction). There were significant reductions in waist circumference (-7.5 ± 4.9 cm, p = 0.001), % fat mass (-9.4 ± 8.3, p < 0.001), total cholesterol (p = 0.026), and triglycerides (p = 0.002).

Conclusions: The use of this weight loss approach was well-received by the study participants. We are currently evaluating whether this approach had a long-term impact on the weight status and quality of life among the study participants.

[Table: see text]
Adolescent intakes of alcohol and folate and risk of proliferative benign breast disease.
Authors: Liu Y. , Tamimi R. M. , Berkey C. S. , Willett W. C. , Collins L. C. , Schnitt S. J. , Colditz G. A.
Published: February 2017

169

Background: Given the importance of exposure between menarche and first childbirth in breast cancer risk, adolescent alcohol consumption may influence the risk of proliferative benign breast disease (BBD). Folate may modify the adverse effect of alcohol on breast cancer.

Methods: We used data from 29,329 women in the Nurses’ Health Study II who completed both adolescent alcohol consumption questions in 1989 and an adolescent diet questionnaire in 1998. A total of 666 women with proliferative BBD between 1991 and 2001 were confirmed by centralized pathology review. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for established risk factors of breast cancer.

Results: Adolescent alcohol consumption was dose-dependently associated with an increased risk of proliferative BBD (HR = 1.12 per 10g/day consumption; 95% CI, 1.03-1.22). There was no significant association with adolescent folate intake. While the interaction between adolescent alcohol and folate intake was not statistically significant, among women with low folate intake (<279 mg/day) the BBD risk was significantly increased with moderate alcohol intake (HR = 1.62; 95% CI, 1.14-2.28) and with high alcohol intake (HR = 1.90; 95% CI, 0.98-3.70; Ptrend <0.01). Adolescent alcohol consumption was not associated with increased risk among women with higher adolescent folate intake.

Conclusions: Adolescent alcohol consumption is associated with higher risk of proliferative BBD, especially in women with low adolescent folate intake.
Use of Blue Citrus, a Chinese herbal remedy, to reduce side effects of aromatase inhibitors.
Authors: Massimino K. , Glissmeyer M. , Wagie T. , Karamlou K. , Look R. M. , Sorenson L. , Turner C. , Johnson N.
Published: February 2017

170

Background: Aromatase inhibitors are widely used in treatment of estrogen receptor positive breast cancer. Many patients experience significant arthralgias, which may lead to early cessation of therapy. Blue Citrus, a mix of Chinese herbs formulated in our community, had anecdotal reports of success in alleviating these symptoms. We objectively evaluated its activity in symptomatic patients.

Methods: Breast cancer patients with significant arthralgia on aromatase inhibitors were enrolled in a prospective fashion to a double blind crossover placebo controlled trial. Each patient received either Blue Citrus (BC+P) or a placebo (P+BC) for three months and then crossed over to the opposite treatment for an additional three months. Symptoms were measured over the course of treatment.

Results: A total of 37 patients enrolled on the study. There were 6 early withdrawals, which left 31 evaluable patients. Visual Analogue Score (VAS) for both groups was similar at baseline at 4.9 and 5.1 for the BC+P and P+BC groups, respectively. At 30 days the BC+P score was 3.4 vs. the P+BC of 4.7 showing clearly improved symptom control in the BC+P group. The P+BC group did however approach the BC+P group by 90 days. At crossover the BC+P group experienced a spike in symptomology when changed to placebo that didn’t appear for the P+BC group. When compared to baseline, mean VAS score on Blue Citrus was 2.98 (p=0.001) versus mean VAS score on placebo 3.92 (p=0.0203). By study end (180 days) the VAS scores for both groups were closer at 2.6 BC+P vs. 3.0 for P+BC but BC+P still maintained lower VAS scores.

Conclusions: Blue Citrus improved symptoms associated with aromatase inhibitor use. Patients who received Blue Citrus in the first arm had rapid improvement in symptoms and experienced return of symptoms when converted to placebo. All patients averaged lower VAS scores on Blue Citrus however at 6 months the difference between the arms became less pronounced.
Change of serum vitamin D according to the breast cancer treatment.
Authors: Kim H. J. , Ahn S.
Published: February 2017

172

Background: Vitamin D deficiency is associated with increased breast cancer risk and decreased breast cancer survival. The purpose of this study was to determine the effect of breast cancer adjuvant treatment to the vitamin D status, as measured by the serum hydroxyvitamin D (25OHD) in breast cancer patients.

Methods: For 589 patients who was diagnosed as a non metastatic breast cancer in 2009 at the asan medical center, blood was prospectively analyzed in batches for serum 25 OHD level at basal and at 6 and 12month. We excluded the patients who took a vitamin D supplementation and got a neoadjuvant chemotherapy. Vitamin D sufficiency was defined as serum as 30ng/ml or greater, insufficiency as 20 to 29 ng/ml and insufficiency as less than 20ng/ml.

Results: At baseline, mean serum 25OHD was greater in summer (April to Oct) than Winter (Nov to May ) (28.2ng/ml vs 32.9ng/ml respectively, p=0.000). The patients who did not get a chemotherapy and anti-hormonal therapy as baseline, the patient with chemotherapy showed decreased serum 25OHD level than who without chemotherapy in 6 month but not in 12 month (p=0.003, vs p=0.156 respectively). The patients who had taken anti-hormonal therapy showed significant increasing serum 25OHD in 6 month and 12 months (p=0.000 both). For the patients who got both chemotherapy and anti-hormonal therapy, the changes of serum 25OHD level is smaller than the patients who got a chemotherapy only. For the patients who got a chemotherapy, 57% of patients were vitamin D sufficient at baseline, but 27% of patients in 6 month and 49% in 12 month (p=0.001).

Conclusions: Vitamin D status was worse during chemotherapy but recovered after chemotherapy. Antihormonal therapy make the serum vitamin D level increased. The translational research about the effect of chemotherapy and antihormonal therapy to the vitamin D status should be warranted.
Pleomorphic lobular breast carcinoma: A review of 35 cases at a single institution.
Authors: Cox J. A. , Eltorky M. A. , Wolski M. J. , Sturgeon J. D. , Joyner M. M. , Markowitz A. B. , Hatch S. S.
Published: February 2017

175

Background: Pleomorphic lobular carcinoma (PL) is an aggressive subtype of invasive lobular carcinoma. A previous report of 52 patients showed an increase in development of metastases for pleomorphic lobular carcinoma patients. There are relatively few case series reporting on this aggressive form of breast cancer. This report features a descriptive and survivorship comparison of a large case series of PL reviewed by a single breast pathologist.

Methods: From 1993-2010 we retrospectively reviewed 198 cases of invasive lobular carcinomas, 35 cases (34 patients with one patient presenting with 2 independent cancers) of PL and 163 cases of non-pleomorphic invasive lobular carcinoma (NPL). The pathology was reviewed by a single breast pathologist and classified as either PL or NPL according to WHO classification. Kaplan-Meier survivals were computed and compared with a log rank test using SPSS 18. Overall survival (OS) was computed from date of diagnosis to date of last update (02/01/11). Progression free survival (PFS) until either local or metastatic failure was also computed.

Results: The median follow-up was 59.5 months and 73 months, for NPL and PL patients respectively. The median age of diagnosis was 55 (range 40-80) and 58.67 (range 36-89) for PL and NPL groups. Of the NPL group, 75.5% were post-menopausal as opposed to 67.6% in the PL group. PL cases were ER positive 87.1% vs. 90.1% of the NPL cases. Her-2/neu status was known in nearly 50% of cases with 17 positive NPL cases and 5 positive PL cases. Clinical stage at presentation was stage IIB or less in 67.6% of the PL patients and 80.1% of the NPL patients. Six patients presented (17.6%) with metastatic disease in the PL group and 12 patients (7.7%) in the NPL group. None of the descriptive comparisons above were significantly different by χ2 analysis. PFS at 5 years was 30% and 21% in PL and NPL patients, respectively (p=0.73). OS at 5 years was 68.5% for PL patients and 83.9% for NPL patients (p=0.031).

Conclusions: In this large case series of PL cases reviewed by a single breast pathologist, PL patients showed a statistically significant decreased OS, but no significant difference in PFS, at 5 years from diagnosis.
Prevalence of BRCA1 mutations in women with triple-negative breast cancer: A systematic review.
Authors: Tun N. M. , Villani G. M. , Ong K.
Published: February 2017

181

Background: We have reported a strong association between “triple-negative” breast cancer (TNBC) [estrogen receptor (ER) and progesterone receptor (PR) negative, HER2 negative] and the risk of having BRCA1 mutations in a meta-analysis. We hereby present a systematic review of a larger pool of specific data investigating the overall prevalence of BRCA1 mutations in women with TNBC.

Methods: A Medline search combining the MeSH terms “BRCA” and “triple” and “negative” yielded 37 articles. A similar search in ASCO abstracts yielded 18 relevant articles. Prevalence in each study population as well as the overall prevalence was calculated.

Results: 13 eligible studies (from year 2006 to 2011) including 1075 women with TNBC were identified. Out of 13, 1 study each was carried out on Ashkenazi Jewish and Hong Kong Chinese women respectively. Overall prevalence of BRCA1 mutations in women with TNBC is 20.93% (225 out of 1075) (range = 4.8%–43%). Ashkenazi Jewish women with TNBC have a higher-than-average prevalence of BRCA1 mutations (29.2%) although it is lower than the prevalence rates of some study populations. A remarkably low prevalence rate of BRCA1 mutations (4.8%) is found in Chinese women with TNBC.

Conclusions: In view of the overall high prevalence rate of BRCA1 mutations (20.93%) in women with TNBC, genetic testing should be discussed with patients with TNBC. Further studies are suggested to evaluate the molecular basis of interestingly low BRCA1 prevalence (4.8%) in Chinese patients with TNBC.
Single institution's data on triple-negative breast cancer in African-American women.
Authors: Abuelgasim Ahmed K. A. , Ghanem Z. Y. , Aggarwal A.
Published: February 2017

188

Background: Although African-American women (AAW) have lower incidence of breast cancer, they have higher breast cancer related mortality compared to Caucasian women (CW). The incidence of triple-negative breast cancer (TNBC) is as high as 20%-26% in AAW compared to 15% in CW. The incidence of TNBC is higher in women younger than age fifty, compared to non-triple-negative breast cancer (NTNBC). TNBC also presents at a more advanced stage. We studied the characteristics of TNBC in AAW diagnosed at Howard University Hospital.

Methods: We identified all the newly diagnosed invasive breast cancer patients who had assessable data for ER, PR, and HER2/neu status from January 2004 to December of 2009, by reviewing our institution’s tumor registry. ER, PR positivity was determined if equal or more than 10% of the tumor cells tested positive by IHC stain. Her-2/neu was determined to be positive if the IHC stain was (3+). Tumors that tested equivocal (2+) were sent for FISH testing. Age and stage data was collected on all patients.

Results: Between Jan 2004 and Dec of 2009, a total of 294 AAW were diagnosed with invasive breast cancer and had enough data for evaluation. Seventy four (25%) patients had TNBC. Among those, 22 patients (30%) were less than 50 years old at the time of diagnosis, compared to 57 patients (26%) of the NTNBC (P-value = 0.5). Fifty two (74%) patients with TNBC were diagnosed with early stage disease (stages 1 and 2), compared to 150 (73%) of the NTNBC (P-value = 1); with 4 patients with TNBC and 15 patients with NTNBC had missing staging. (See table.)

Conclusions: The incidence of TNBC in our cohort of AAW is 25% which is the same as the incidence reported in the literature. Even though TNBC patients are known to have worse prognosis, this may not be attributed to the stage of the disease at presentation or the age of the patient since both group showed no statistically significant difference in both variables.

[Table: see text]
Ethnic disparity of treatment initiation in women diagnosed with breast cancer.
Authors: Omaira M. , Mozayen M. , Mushtaq R. , Katato K.
Published: February 2017

189

Background: Despite the major advances in early detection and treatment of breast cancer (BC), African American women, continued to have a higher mortality rates than Caucasians. Many studies have failed to identify a key factor to explain racial disparities in breast cancer outcome. These disparities persist even after controlling for insurance and socioeconomic settings. Data about delays in treatment initiation are limited and inconclusive. We intend to compare the time from diagnosis to the initiation of treatment between African American and Caucasian women diagnosed with BC in a single community-based cancer registry.

Methods: Women aged 18 to 64 years with breast cancer were identified, between 1993 and 2009, using data from the Tumor Registry at Hurley Medical Center in Flint, Michigan. Patient’s characteristics obtained include age at diagnosis, race, stage, date of diagnosis, and date of treatment initiation. All patients were previously insured or became insured after diagnosis. Time from diagnosis to the initiation of treatment was calculated in days and compared between African American and Caucasian women using t-test.

Results: A total of 1016 patients have been identified with diagnosis of BC. 23 patients were excluded due to missing data. 993 patients were analyzed. African Americans were 355 (36%), Caucasians 617 (62%), and other ethnicities 21 (2%). Mean age at diagnosis was (48.9) for African Americans versus (51.45) for Caucasians (p = 0.005). African American women were more likely to present with advanced stage (III, IV) than Caucasians (18% versus 12%, p = 0.009). African American women had significant delay in the treatment initiation of BC compared to Caucasians (31.11 versus 21.52 days, p < 0.0001).

Conclusions: African American women were diagnosed with breast cancer at younger age and more advanced disease than Caucasians. African American women experienced significant delay in the initiation of therapy after diagnosis compared to Caucasians. However, the impact of an average delay of 10 days in treatment on overall survival is unknown. The exact explanation of this disparity is yet to be determined.
Microarray-based gene expression profiles to predict ELISA-derived uPA and PAI-1 levels in breast cancer biopsies: A comparison between fresh frozen (FF) and formalin-fixed, paraffin-embedded (FFPE) samples.
Authors: Matuschek C. , Prisack H. B. , Boelke E. , Budach W. , Janni W. , Rezai M. , Bojar H.
Published: February 2017

194

Background: The urokinase plasminogen-activator (uPA) and its inhibitor (PAI-1) predict the benefit of node-negative breast cancer patients from chemotherapy. The determination of uPA and PAI-1 need(s) large amounts of tumor tissue. In contrast, microarray-based gene expression profiling (MGEP) requires only small quantities of FF tissue and is applicable to FFPE archival tissue. Identification of MPEG-derived surrogate markers for ELISA-based uPA/PAI-1 may facilitate their analysis together with MPEG-based predictive genes and metagenes.

Methods: Three groups of breast cancer biopsies were analysed. Group A: 136 FF tissues from 2008-2009, group B: 85 FF tissues from 2010, group C: 20 independent FFPE tissues. Gene expression was assessed by Agilent 4x44K microarrays.

Results: For group A a significant correlation between protein expression of uPA and uPA gene (PLAU) expression (r = 0.627 p < 0.001) and PAI-1 and PAI-1 genes (SERPINE1)(r = 0.281 p = 0.001) was found. Top sets of genes correlated with uPA/PAI-1 protein expression were extracted. For group B additional sets of top correlated genes were identified. The correlation of individual genes with uPA/PAI-1 protein expression was highest for their genes themselves (PLAU: r = 0.694 p < 0.001; SERPINE1 (r = 0.469 p < 0.001). Subsequently consensus gene sets were identified with a good performance for both biopsy sets. Only genes which were significantly correlated with their counterparts in group C were selected, resulting in a final 11-gene model (uPA metagene) and a 6-gene model (PAI-1 metagene). They significantly correlated with uPA/PAI-1 protein expression in all groups of biopsies (uPA: group A: r = 0.621, p < 0.001; group B: r = 0.771, p < 0.001; group C: r = 0.665, p = 0.005; for PAI-1: group A: r = 0.569, p < 0.001; group B: r = 0.687, p < 0.001; group C: r = 0.683, p = 0.008).

Conclusions: Reliable MPEG-derived metagenes as surrogate markers for ELISA-based uPA/PAI-1 expression were identified.
Geographic disparity in the use of surgical management (SM) and radiotherapy (RT) for female breast cancer (BC) in Wisconsin (WI).
Authors: Ho A. , White J. R. , Owen J. B. , Trentham-Dietz A. , Wilson J. F.
Published: February 2017

209

Background: The WICaRE Program is a part of the cross sectional Patterns of Care Study–Breast and Prostate (PoC-BP) that sought to evaluate the patterns of BC care in the state WI and to identify areas for potential improvement in data collection and factors associated with variation in care. This study was to examine the geographic disparities in SM and the use of RT in female BC patients diagnosed in WI in 2004.

Methods: The Wisconsin Cancer Reporting System (WCRS) receives reports from 130+ facilities. Information of patient (disease status, sociodemographic, treatment, county of residence) was obtained from cancer registries and supplemental data was reabstracted from medical charts across 66 counties. Geographic regions were counties grouped by WI Dept. of Health Services (DHS) as Northeastern (NE), Northern (N), Southeastern (SE), Southern (S), Western (W).

Results: A total of 1037 cases were reported. 25% age 20-49, 49% age 50-69, and 28% age 70+; Caucasian had 82%, black 10% and others 8%. 34% had T1 stage, 9% T2, 4% T3+, and 53% TX-T0/unknown stage. 46% had reported mild comorbidity, 9% had moderate or severe comorbidity. Majority (73%) lived in the Metropolitan Statistical Area (MSA). 29% patients from NE region, 10% from N, 36% SE, 17% S and 8% W. Patients in the S and W had significantly lower % who received RT (46 and 48% respectively) than those in NE (61%), N (62%) and SE (63%), p=0.01; % mastectomy (MA) by regions were 43% (NE), 42% (N), 33% (SE), 47% (S) and 35% (W), p=0.009. Multivariate models adjusting for disease status, comorbidity, and sociodemographic factors showed that patients in MSA region were more likely to have RT compared to those in non-MSA (odds ratio, OR=1.66, 95%CI=1.14-2.40), but those in S were less likely than those in SE (OR=0.59, 95%CI=0.38-0.91). Patients in MSA had a decreased likelihood of undergoing mastectomy. NE (OR=1.6, 95%CI=1.08-2.29) and S (OR= 2.04, 95%CI=1.31-3.17) had significantly higher odds of having MA than those in SE.

Conclusions: This study showed evidence of geographic disparity in medical care for BC patients in Wisconsin. Identifying factors mediating this disparity will help in developing appropriate treatment options and improving outcomes.
Breast cancer treatment resources and guideline-concordant treatment in Appalachia.
Authors: Yao N. , Hillemeier M. M. , Anderson R. T.
Published: February 2017

216

Background: Appalachia has poorer cancer outcomes, but little research has been done regarding availability of cancer care resources in this region and how resource availability may relate to cancer outcomes. This study 1) examines associations between radiation therapy resources and receipt of radiotherapy after BCS in counties within Kentucky - a SEER state; and 2) describes spatial patterning of breast cancer treatment resources in all 13 Appalachian states.

Methods: For the Kentucky analyses, county-level data from the Area Resource File and SEER registry are analyzed. Bivariate analyses and spatial lag regression using a 6-nearest neighboring counties matrix are conducted. The sample includes stage I or II primary breast cancer patients age 18+ years diagnosed in Kentucky during 2000-2007. The dependent variable is the county-level percentage of patients received BCS without radiation; independent variables include density of radiation therapy providers and facilities and other socioeconomic covariates. For the analyses of entire Appalachian region, descriptive analyses and exploratory spatial data analysis are conducted including 420 Appalachian counties and 644 non-Appalachian counties in 13 states.

Results: In Kentucky 16.44% of 17,227 early stage breast cancer patients received BCS without radiation therapy (21.08% in Appalachia versus 14.80% in non-Appalachia, p<0.001). Appalachian Kentucky had significantly fewer radiation oncologists and radiation therapy facilities per capita than non-Appalachian Kentucky. The number of radiation therapy facilities per capita is negatively associated with rates of BCS without radiation when controlling for covariates. Analysis of 13 Appalachian states shows that Appalachian counties, especially in the Central and Southern regions, had significant fewer physicians per capita in Surgery, Anesthesia, Clinical Pathology, and Radiation Oncology. Clustering of scarce breast cancer care resources was observed in Central Appalachia.

Conclusions: Appalachian counties, especially in central Appalachia, have fewer breast cancer treatment resources than non-Appalachian counties, and resource availability is associated with cancer health disparities.
Predictive factors of adjuvant therapy-related amenorrhea for patients with breast cancer.
Authors: Tamura N. , Kato T. , Shimizu C. , Kinoshita T. , Fujiwara Y.
Published: February 2017

217

Background: Reproductive age breast cancer patients often experience therapy-related amenorrhea so preserving fertility after treatment is a major concern. Anti-mullerian hormone (AMH) values have been reported useful in predicting menopause for infertility treatment patients, but published information is limited regarding breast cancer patients. If amenorrhea can be predicted before treatment, breast cancer patients hoping to have children in the future can consider this information in choosing treatment. Our aim was to predict patient fertility using AMH values.

Methods: Forty breast cancer patients, 25-45 years of age (median, 35.5), who received adjuvant chemotherapy (CT) or endocrine therapy (ET), had AMH values retrospectively assayed from frozen serum before and after treatment. AMH values were then analyzed in relation to clinicopathological factors using logistic analysis. Of 19 adjuvant CT patients whose AMH values could be assayed, Cox’s proportional hazard model indicated a correlation in terms of amenorrhea and time to menses resumption between clinicolpathological factors and AMH values.

Results: The mean pretreatment AMH value for all 40 patients was 21.4pM (range, 3-78) and a correlation was demonstrated with patient age, but not breast cancer intrinsic subtype or stage. AMH values decreased to the lower limit after treatment for all CT patients regardless of age, but there was a difference in degree depending on patient age for ET patients. Of the 19 CT patients, the mean AMH value was 25.6pM (3-78). These patients all underwent a regimen of anthracycline with 11 (58%) also receiving a regimen of taxiane. After starting CT, 17 patients (89%) experienced amenorrhea, but 11 (59%) resumed menstruation within one year of finishing CT and 15 (78%) resumed within two years. There were no significant differences among CT patients in age, pretreatment AMH value, intrinsic subtype or stage, but patients receiving taxiane demonstrated a noteworthy trend.

Conclusions: Although we were unable to predict menopause directly using AMH values given the small number of patients in this study, we could estimate the risk of menopause as being either low or high for CT patients based on age and type of regimen.
A nonrandomized observational trial of short-term preoperative endocrine therapy in ER-positive breast cancer to investigate change in genomic expression using the 21-gene breast cancer assay.
Authors: Bleznak A. D. , Dellers E. A. , Glenn-Porter B. , Kimmel S. , Chung H. , Yoshizawa C. , Burke E. , Davison D. S. , Chao C.
Published: February 2017

221

Background: Preoperative systemic treatment is commonly employed for women with locally advanced breast cancer. Women with early-stage breast cancer, whose resections may be delayed for 30 to 60 days while they undergo preoperative evaluation, may benefit from receiving preoperative endocrine therapy while awaiting surgery. One rationale for not initiating such treatment is that the cancer may be rendered less chemosensitive. The 21-gene assay is a proven predictor of chemotherapy responsiveness. The objective of this study is to examine the association between recurrence score (RS) and ER, PR, and HER2 RT-PCR values in core biopsy and surgical specimens from patients treated with short term pre-operative endocrine therapy.

Methods: Pre- and postmenopausal women with clinical T1-N0-M0, sonographically visible, ER-positive, HER2-negative breast cancer were eligible. Patients were treated with 4-8 weeks of preoperative endocrine therapy; letrozole if postmenopausal or tamoxifen if premenopausal. Clinical breast examination and ultrasound were conducted every two weeks, with the final ultrasound immediately prior to surgery. Tumor blocks from the core biopsy and surgical excision were submitted to Genomic Health, Inc., where RS, ER, PR, and HER2 results were obtained from each of the paired specimens.

Results: Nineteen matching core biopsy and surgical specimens were available for analysis. Pearson correlation coefficients between core biopsy and excisional sample results were 0.89 for RS, 0.87 for ER, 0.72 for PR, and 0.77 for HER2. On average, small but statistically significant increases in RS and decreases in ER and PR were observed (all p < 0.005 from paired t-test). No obvious associations between these markers and clinical response were observed.

Conclusions: In this small, hypothesis-generating study, paired RS and RT-PCR for ER/PR/HER2 remained correlated after short-term preoperative endocrine therapy. This study provides no suggestion of decreasing chemosensitivity during preoperative endocrine therapy, but additional research is warranted to explore these findings further.