Stage Invasive Breast Cancer Research Articles

Abstract B64: Development and analytical validation of a fully-automated platform for quantification of MetaSites to predict systemic metastasis

Abstract Background: Tumor metastasis is responsible for the majority of solid tumor related deaths. Diagnostic assays that accurately predict risk of cancer dissemination provide useful information for optimizing personalized treatment strategies. As previously demonstrated, using manual methods, the number and distribution of MetaSites in the tumor microenvironment significantly predicts metastatic disease in patients with ER-positive early stage invasive breast cancer. A MetaSite is the juxtaposed multicellular structure comprised of a blood vessel, the macrophage immune cell, and an invasive tumor cell. To reduce pathologist counting variability, an objective and reproducible automated laboratory process workflow to identify and quantify MetaSites for a clinical grade assay was developed. Methods: Digital pathology imaging coupled with image analysis tools was employed to develop a fully-automated, objective method and workflow for quantification of MetaSites in formalin-fixed paraffin embedded tumor samples. Using this method, areas for analysis and quantification of MetaSites were automated by integrating high resolution automated microscopy with multiple image analysis algorithms. A pathologist ensured overall diagnostic quality of the sample in addition to approving individual images for MetaSite scoring. Results: In this analytical validation study, the platform was demonstrated to be greater than 97% reproducible with a mean coefficient of variation of 6.6% (n=35) for 3 independent measurements of the same slide. Further, MetaSite scores showed correlation coefficients (Pearson's R) greater than 0.98 between measurements with no significant difference in absolute values by repeated measures analysis. Importantly, MetaSite scores on independently stained tumor sections showed greater than 90% reproducibility, indicating minimal heterogeneity within the tumor with respect to MetaSite score, section to section. Additionally, day-to-day MetaSite scores showed correlation coefficients (Pearson's R) greater than 0.90 between staining runs with no significant difference in mean MetaSite scores. Conclusion: Taken together, these data demonstrate the successful development and analytical validation of a fully-automated, highly reproducible MetaSite quantification platform. With development and analytical validation of this test, it is now possible to provide physicians with information regarding the aggressiveness of patient tumors and accurate prediction of cancer metastasis. This method is being further validated in a large (n=481) case control clinical study. Citation Format: Michael Peterson, Lonnie Graves, Michael J. Donovan, Douglas Hamilton, Olga Poxdnyakova, Mark Gustavson. Development and analytical validation of a fully-automated platform for quantification of MetaSites to predict systemic metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr B64.

Lifestyle and breast cancer recurrences: the DIANA-5 trial.

The DIANA (Diet and Androgens)-5 study is a multi-institutional randomized controlled trial of the effectiveness of a diet based on Mediterranean and macrobiotic recipes and principles, associated with moderate physical activity, in reducing additional breast cancer events in women with early stage invasive breast cancer at high risk of recurrence because of metabolic or endocrine milieu. The intervention is expected to reduce serum insulin and sex hormones, which were associated with breast prognosis in previous studies. Between 2008 and 2010, the study randomly assigned 1208 patients to an intensive diet and exercise intervention or to a comparison group, to be followed-up through 2015. General lifestyle recommendations for the prevention of cancer are given to both groups, and the intervention group is being offered a comprehensive lifestyle intervention, including cooking classes, conferences, common meals and exercise sessions. Adherence assessments occurred at baseline and at 12 months and are planned at 36 and 60 months. They include food frequency diaries, anthropometric measures, body fat distribution assessed with impedance scale, one week registration of physical activity with a multisensor arm-band monitor, metabolic and endocrine blood parameters. Outcome breast cancer events are assessed through self report at semi annual meetings or telephone interview and are validated through medical record verification. The randomized groups were comparable for age (51.8 years), proportion of ER-negative tumors (22%), axillary node metastasis (42%), reproductive variables, tobacco smoking, blood pressure, anthropometric measurements and hormonal and metabolic parameters. DIANA-5 has the potential to establish whether a Mediterranean-macrobiotic lifestyle may reduce breast cancer recurrences. We will assess evidence of effectiveness, first by comparing the incidence of additional breast cancer events (local or distant recurrence, second ipsilateral or contralateral cancer) in the intervention and in the control group, by an intention-to-treat analysis, and second by analyzing the incidence of breast cancer events in the total study population by compliance assessment score.

Lipoprotein subfractions by nuclear magnetic resonance are associated with tumor characteristics in breast cancer.

BackgroundHigh-Density Lipoprotein (HDL)-cholesterol, has been associated with breast cancer development, but the association is under debate, and whether lipoprotein subfractions is associated with breast tumor characteristics remains unclear.MethodsAmong 56 women with newly diagnosed invasive breast cancer stage I/II, aged 35–75 years, pre-surgery overnight fasting serum concentrations of lipids were assessed, and body mass index (BMI) was measured. All breast tumors were immunohistochemically examined in the surgical specimen. Serum metabolomics of lipoprotein subfractions and their contents of cholesterol, free cholesterol, phospholipids, apolipoprotein-A1 and apolipoprotein-A2, were assessed using nuclear magnetic resonance. Principal component analysis, partial least square analysis, and uni- and multivariable linear regression models were used to study whether lipoprotein subfractions were associated with breast cancer tumor characteristics.ResultsThe breast cancer patients had following means: age at diagnosis: 55.1 years; BMI: 25.1 kg/m2; total-Cholesterol: 5.74 mmol/L; HDL-Cholesterol: 1.78 mmol/L; Low-Density Lipoprotein (LDL)-Cholesterol: 3.45 mmol/L; triglycerides: 1.18 mmol/L. The mean tumor size was 16.4 mm, and the mean Ki67 hotspot index was 26.5 %. Most (93 %) of the patients had estrogen receptor (ER) positive tumors (≥1 % ER+), and 82 % had progesterone receptor (PgR) positive tumors (≥10 % PgR+). Several HDL subfraction contents were strongly associated with PgR expression: Apolipoprotein-A1 (β 0.46, CI 0.22–0.69, p < 0.001), HDL cholesterol (β 0.95, CI 0.51–1.39, p < 0.001), HDL free cholesterol (β 2.88, CI 1.28–4.48, p = 0.001), HDL phospholipids (β 0.70, CI 0.36–1.04, p < 0.001). Similar results were observed for the subfractions of HDL1-3. We observed inverse associations between HDL phospholipids and Ki67 (β -0.25, p = 0.008), and in particular between HDL1’s contents of cholesterol, phospholipids, apolipoprotein-A1, apolipoprotein-A2 and Ki67. No association was observed between lipoproteins and ER expression.ConclusionOur findings hypothesize associations between different lipoprotein subfractions, and PgR expression, and Ki 67 % in breast tumors. These findings may have clinical implications, but require confirmation in larger studies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12944-016-0225-4) contains supplementary material, which is available to authorized users.

Abstract C25: The effect of longitudinal symptom distress and overall cancer distress on the ability of African American women to receive prescribed breast cancer chemotherapy without delay

Abstract Background: Racial breast cancer survival disparity is attributed, in part, to disparity in breast cancer treatment. Cancer related distress and symptom incidence and associated distress is historically higher than comparative white women during breast cancer chemotherapy and may influence the ability of African American women to receive full dose and timely chemotherapy. Therefore symptom incidence, distress and overall cancer related distress may be under recognized as a potential etiology of racial survival disparity. Objective: To describe the incidence and severity of symptoms and overall cancer-related distress in African American women and the association of symptom and cancer-related distress to adherence (receiving full dose prescribed without delay) to prescribed chemotherapy over three time points (baseline, midpoint and completion). Methods: A descriptive, correlational analysis was conducted of longitudinal data from a recently completed randomized controlled trial of a psycho-educational intervention entitled the Adherence, Communication, Treatment and Support (ACTS) to encourage adherence to chemotherapy for African American women with breast cancer. In the ACTS Trial we assessed symptom incidence and severity and overall cancer-related distress as potential moderators of women's willingness and/or ability to receive timely and full dose chemotherapy. We measured change of symptom incidence and severity and cancer-related distress at three time points: pre-chemotherapy (Time 1); midpoint of chemotherapy (Time 2) and completion of chemotherapy (Time 3). The Cancer Distress Thermometer (DT) was used to measure cancer-related distress; the total number of symptoms (TOTNS) and the McCorkle Symptom Distress Scale (SDS) total score were to measure symptom incidence and severity, respectively. Adherence data in terms of the number of days delayed related to the patient, clinician, and overall were extracted from medical records. Random coefficient modeling was used for analysis to accommodate the variability in the timing of treatment cycles at the key time points. Results: Subjects (n=142) were diagnosed with any stage invasive breast cancer and were undergoing chemotherapy. Results were based on 131 patients with evaluable data over at least two time points. DT, SDS, and TOTNS significantly changed over time suggesting that SDS and TOTNS increases linearly over time (SDS: b1=0.03324, p&amp;lt;.001; TOTNS: b1=0.02686, p&amp;lt;.001), whereas DT showed a slight decrease (b1=-0.00414, p=.044). Overall cancer-related distress was not significantly associated with clinical delays but was positively related to patient delays (b1=0.2445, p=.034) and total delays (b1=0.5445, p=.018). Overall total number of symptoms and symptom distress was positively related to clinical delays (b1=0.1438, p=.037) and total delays (b1=0.1669, p=.044). Conclusions: Worsening in number of symptoms, overall cancer-related distress and symptom distress over the course of chemotherapy was demonstrated among African American women receiving breast cancer chemotherapy. Worsening symptom and cancer-related distress was associated with lack of ability to receive full dose chemotherapy at the prescribed time. Implications for Practice: The influence of total number of symptoms, symptom distress and overall cancer-related distress on chemotherapy treatment delays is evident among this cohort of African American women receiving chemotherapy. Clinically this emphasizes the importance of close monitoring of cancer-related distress and symptom incidence and severity among African American women in order to allow timely breast cancer chemotherapy. Citation Format: Melissa K. Yee, Susan Sereika, Margaret Quinn Rosenzweig. The effect of longitudinal symptom distress and overall cancer distress on the ability of African American women to receive prescribed breast cancer chemotherapy without delay. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr C25.

Abstract PD4-01: Longitudinal health related quality of life (HRQOL) and subsequent adherence to breast cancer chemotherapy among African American women

Abstract Background: Racial breast cancer survival disparity is attributed, in part, to disparity in cancer treatment. Changes in HRQOL influencing treatment adherence over the chemotherapy course may be under recognized as a potential etiology of racial disparity in breast cancer treatment. Objective: To describe African American breast cancer women's HRQOL and the relationship of HRQOL with adherence (dose prescribed without delay) rates to prescribed chemotherapy over three time points of chemotherapy (baseline, midpoint and completion). Methods: Descriptive analysis of an ongoing randomized controlled trial of a psycho-educational intervention to encourage acceptance and adherence to chemotherapy for African American women with breast cancer. The present study used HRQOL data from the parent study and descriptively reported change of quality of life over three time points: baseline – pre chemotherapy (Time 1); at midpoint of chemotherapy (Time 2) and at completion of chemotherapy (Time 3). A further analysis of HRQOL and its role as a potential mediator with treatment adherence was assessed. Descriptive analysis of secondary aim of the parent study, The Attitudes, Communication, Treatment and Support (ACTS) intervention. The Functional Assessment of Cancer Therapy (FACT) was used to measure HRQOL including physical, social, functional and emotional subscales. Adherence data were extracted from medical records. Linear mixed modeling analysis method was used. Results: One hundred and twenty six African American patients were included from the ongoing parent study for this analysis, 67 from the intervention group and 69 from the usual care group. Subjects were recruited from four cancer centers in western Pennsylvania and one from Western Ohio. Subjects were diagnosed with any stage invasive breast cancer and were undergoing chemotherapy. Overall HRQOL decreased significantly over three time points (p&amp;lt;0.01) primarily driven from the physical subscale. Adherence to prescribed chemotherapy was significantly correlated with HRQOL (r=0.32, p&amp;lt;0.01). Physical well-being subscales decreased significantly over time. Energy, treatment side effects, feeling ill and spending time in bed during chemotherapy were items that decreased in score (increased in severity) most over three time points (decreased score &amp;gt;0.5 from time1 to time3). Energy and pain were the items with the lowest scores for the physical well-being subscale at baseline and the two follow up assessments (mean score&amp;lt;3.0 out of 4). Conclusions: Worsening in physical symptoms and functional status was demonstrated over time among African American women receiving breast cancer chemotherapy. Lack of adherence to prescribed chemotherapy was significantly correlated with declining HRQOL. Implications for Practice: The influence of HRQOL on chemotherapy dose reduction and early treatment cessation was primarily from physical factors during chemotherapy for African American women. Clinically this emphasizes the importance of close QOL and symptom screening, encouraging symptom reporting and the need to exhaust symptom management options before early treatment termination. Citation Format: Rosenzweig MQ, Liang Z. Longitudinal health related quality of life (HRQOL) and subsequent adherence to breast cancer chemotherapy among African American women. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr PD4-01.

Abstract OT2-05-02: Characterization of the oral, gut, and breast tissue microbiomes in women with invasive breast cancer, ductal carcinoma in situ (DCIS), or no history of breast cancer

Abstract Background: We now know that there is an interplay between our bodies and the bacteria that we carry, both in health and in disease. Inflammatory diseases associated with disruptions in microbial equilibria, such as periodontal disease and ulcerative colitis, as well as chronic antibiotic use, have been associated with increased risk for cancer development. In a previous small pilot study, we observed differences in the oral microbiomes of women with breast cancer and healthy women. This presentation describes an ongoing study in which we aim to validate our previous findings in a larger cohort of women, as well as extend the microbiomes studied to include the gut and local breast tissue microbiota. Trial design and eligibility criteria: Women with invasive breast cancer or with ductal carcinoma in situ (DCIS) who have not received prior therapy for their disease are eligible for enrollment. A cohort of healthy women will also be enrolled. Sample collection kits containing cheek and stool swab materials are distributed to patients in the clinic, and breast tumor tissue is collected at the time of surgery. Specific aims: 1. To characterize and compare oral and gut microbial diversity from women with early stage invasive breast cancer, women with DCIS, and healthy women; and 2. To characterize the microbiota associated with breast tumor tissue and compare this to healthy breast tissue. Methods: DNA from the three sites is isolated, the bacterial 16S rRNA gene is PCR amplified and sequenced, and the bacterial species present are enumerated. Oral, gut, and breast tissue microbial diversity at the genus and species levels will be assessed using the Shannon diversity index. Student's t-test will be used to compare the mean diversity index values. Evaluation of microbial diversity and clinical variables will be determined using Spearman or Pearson correlations depending on the distribution of the data. We will also compare oral microbial diversity and clinical variables across racial and ethnic groups to determine if differences in the microbiomes may explain disparities in incidence across these groups. Classification and regression trees (CART) will be employed to develop rule sets based on the abundance of oral bacteria that discriminate breast cancer vs. DCIS vs. healthy controls. Present accrual: As of June, 2015, 32 women with early-stage invasive cancer, 8 women with DCIS, and 9 healthy women received sample collection kits. Breast tumor tissue has been collected from 11 invasive breast cancer cases and 2 DCIS cases. Target accrual: For the oral and gut microbiome analyses: 100 women with early-stage invasive breast cancer, 100 women with ductal carcinoma in situ (DCIS), and 100 healthy women with no history of breast cancer. For the breast tissue microbiome analyses: 20 women with invasive breast cancer, 10 patients with DCIS, and 10 reduction mammoplasty cases from healthy women. Citation Format: Campbell M, O'Meara T, Esserman LJ. Characterization of the oral, gut, and breast tissue microbiomes in women with invasive breast cancer, ductal carcinoma in situ (DCIS), or no history of breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT2-05-02.

Abstract PD4-05: Complementary and alternative medicine use and breast cancer chemotherapy initiation: The BQUAL study

Abstract PURPOSE: Adjuvant therapy is associated with improved survival for women with breast cancer, but not all women who could benefit initiate treatment. Women's belief systems are related to treatment initiation. It has been hypothesized that complementary and alternative (CAM) use is associated with decreased initiation of standard oncology treatments because patients may be exploring alternative treatment approaches. However, there are limited data on the association between CAM use and cancer treatment initiation. We examined the association between CAM use and initiation of adjuvant breast cancer chemotherapy in a prospective cohort of early stage breast cancer patients. PATIENTS AND METHODS: Subjects participated in a multi-center prospective cohort study of women with early stage invasive breast cancer (n=1,156). National Comprehensive Cancer Network guidelines were used to define groups based on whether chemotherapy was indicated. Three subgroups were created: chemotherapy indicated for subjects &amp;lt;70 years, chemotherapy discretionary for subjects &amp;lt;70 years, and chemotherapy discretionary for subjects ≥70 years. CAM use was assessed based upon self-reported use of 5 CAM modalities, including vitamin/mineral supplements, herbal supplements, other over-the-counter natural products, mind-body based approaches, and body/energy-based treatments. Psychosocial factors potentially related to chemotherapy initiation were assessed. Multivariable logistic regression models evaluated the associations between CAM use and chemotherapy initiation, adjusted for demographic, clinical and psychosocial factors. RESULTS: Current CAM use was reported by 87% of women and 38% reporting current use of ≥3 modalities. The most commonly used CAM modalities were mind body therapies (63%) and other natural products (41%). In bivariate analyses, among women &amp;lt;70 years where chemotherapy was indicated, women who reported current use of vitamins/minerals or current use of all 5 CAM modalities were less likely to initiate chemotherapy compared to non-users (P&amp;lt;.0001), but this was not observed among women for whom chemotherapy was discretionary. Psychosocial factors were also associated with high levels of current CAM use in this group, including higher expectations of adverse effects from chemotherapy, more concerns about the physical effects of chemotherapy, lower beliefs in the benefits of chemotherapy, and lower positive decision balance while making chemotherapy decisions (all P&amp;lt;.05). Among women age &amp;lt;70 years for whom chemotherapy was indicated, 89% initiated treatment, and current use of all 5 CAM modalities was inversely associated with initiation in multivariable analyses adjusted for demographic and clinical factors (OR=0.08, CI: 0.02-0.32). The association remained after separately adjusting for psychosocial factors (all P&amp;lt;.05), except for positive decision balance, which was no longer statistically significant. CONCLUSIONS: High use of CAM was associated with decreased chemotherapy initiation among women with breast cancer for whom chemotherapy was indicated. It is important for oncologists to discuss CAM use with their patients, especially since high CAM use is associated with negative expectations and beliefs about chemotherapy. Citation Format: Greenlee H, Neugut AI, Falci L, Hillyer GC, Buono D, Roh JM, Ergas IJ, Kwan ML, Lee M, Tsai WY, Shi Z, Lamerato L, Mandelblatt JS, Kushi LH, Hershman DL. Complementary and alternative medicine use and breast cancer chemotherapy initiation: The BQUAL study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr PD4-05.

Estrogen-Receptor, Progesterone-Receptor and HER2 Status Determination in Invasive Breast Cancer. Concordance between Immuno-Histochemistry and MapQuant™ Microarray Based Assay.

BackgroundHormone receptor status and HER2 status are of critical interest in determining the prognosis of breast cancer patients. Their status is routinely assessed by immunohistochemistry (IHC). However, it is subject to intra-laboratory and inter-laboratory variability. The aim of our study was to compare the estrogen receptor, progesterone receptor and HER2 status as determined by the MapQuant™ test to the routine immuno-histochemical tests in early stage invasive breast cancer in a large comprehensive cancer center.Patients and MethodsWe retrospectively studied 163 invasive early-stage breast carcinoma with standard IHC status. The genomic status was determined using the MapQuant™ test providing the genomic grade index.ResultsWe found only 4 tumours out of 161 (2.5%) with discrepant IHC and genomic results concerning ER status. The concordance rate between the two methods was 97.5% and the Cohen’s Kappa coefficient was 0.89.Comparison between the MapQuant™ PR status and the PR IHC status gave more discrepancies. The concordance rate between the two methods was 91.4% and the Cohen’s Kappa coefficient was 0.74.The HER2 MapQuant™ test was classified as « undetermined » in 2 out of 163 cases (1.2%). One HER2 IHC-negative tumour was found positive with a high HER2 MapQuant™ genomic score. The concordance rate between the two methods was 99.3% and the Cohen’s Kappa coefficient was 0.86.ConclusionOur results show that the MapQuant™ assay, based on mRNA expression assay, provides an objective and quantitative assessment of Estrogen receptor, Progesterone receptor and HER2 status in invasive breast cancer.

Risk Factors Associated with Sentinel Lymph Node Biopsy in Patients with a Preoperative Diagnosis of Ductal Carcinoma &amp;lt;i&amp;gt;In Situ&amp;lt;/i&amp;gt;

Purpose: Sentinel lymph node (SLN) biopsy has become the gold standard for axillary staging of invasive breast cancer. However, some controversy has existed concerning the usefulness of SLN biopsy in ductal carcinoma in situ (DCIS). In this study, we tried to identify the usefulness of SLN biopsy in patients with an initial preoperative diagnosis of DCIS. Methods: A retrospective analysis was performed using single-center data of 415 patients with an initial diagnosis of DCIS between January 2003 and December 2013. Many features were correlated with upstaging and positive SLN biopsy using univariate analysis and multivariate analysis. Results: A total of 415 patients with a preoperative diagnosis of DCIS were enrolled in this study. Total 320 of 415 patients (77.1%) underwent axillary evaluation via SLN biopsy, axillary lymph node dissection, or additional axillary lymph node dissection, and 24 of 320 patients (7.5%) were diagnosed with axillary lymph node metastasis or micrometastases in the lymph nodes. Of 415, 296 patients (71.3%) underwent SLN biopsy and 16 patients (5.4%) had positive SLN biopsy. The rate of upstaging to invasive cancer was 4.1% (17 of 415 patients) on final pathology. Of the 17 patients who were upstaged to invasive carcinoma at final pathology, seven patients (41.2%) had a positive SLN biopsy. The statistically significant factors of upstaging were large tumor size (≥2 cm), histologic features of intermediate or high-grade tumor, and positive SLN biopsy. Conclusion: SLN biopsy should be considered in patients with high risk DCIS as a part of the primary surgical procedure. Keywords: Breast; Noninfiltrating intraductal carcinoma; Sentinel lymph node biopsy

Weekly Concomitant Boost During Whole-Breast Hypofractionated Radiation Therapy: A Feasibility and Toxicity Study

Weekly Concomitant Boost During Whole-Breast Hypofractionated Radiation Therapy: A Feasibility and Toxicity Study

Contrast-enhanced ultrasound -guided axillary lymph node core biopsy: Diagnostic accuracy in preoperative staging of invasive breast cancer

ObjectivesTo evaluate accuracy of contrast enhanced ultrasound (CEUS)-sentinel procedure followed by core biopsy (CB) and marking in patients with breast cancer. To compare the axillary metastatic tumour burden in patients with positive vs. negative CB results. MethodsTwo radiologists in our tertiary care hospital performed axillary CEUS sentinel procedures on consecutive US node negative breast cancer patients. The first enhancing lymph node (LN) was core biopsied and marked with a breast coil. The results were compared to final histopathology. We analysed the diagnostic performance of CEUS CB and its ability to detect patients with higher axillary burden (>2 metastasis). ResultsDuring the study period between January 2013 and December 2014, altogether 54 patients (mean age 60.4 years) were included in the statistical analysis. The sensitivity for CEUS CB was 66.7%, specificity 100%, PPV 100%, NPV 93.8% and overall accuracy 94.4%. The method correctly recognised all the axillae with higher tumour burdens (sensitivity 100%, N=3) and 59.3% of coils marking the LNs were discovered. ConclusionCEUS -guided axillary CB proved to be feasible and accurate procedure with moderate sensitivity and it clearly identified the higher axillary tumour burden. The coil marking of LNs as used cannot be recommended. In clinical routine, CEUS procedure might be recommended in selective patient populations.

Complete Regression of Ductal Carcinoma in Situ Following Chemotherapy and Trastuzumab: Should we Rethink Management?

Background: Ductal carcinoma in situ (DCIS) includes comedo-DCIS, which consists of high-grade DCIS associated with dilated ducts filled with intraluminal comedonecrosis. Current consensus opinion is that prognosis is excellent for all forms of DCIS and that no form of DCIS responds to chemotherapy. However, herein we describe a patient who had complete resolution of comedo-DCIS with the combination of paclitaxel, carboplatin and trastuzumab and results of a retrospective analysis that challenge current opinion. Materials and methods: The cancer registry of Hoag Hospital in Newport Beach, California, was used to indentify subset cohorts of patients with DCIS and local- stage invasive breast cancer. Survival curves were compared by the log-rank test. Results: There were 7,373 breast cancer patients diagnosed during 1983-2007 including 205 classified as comedo-DCIS, 1006 as non-comedo-DCIS, 46 as locally invasive comedocarcinoma and 3905 as other types of locally invasive breast cancer. Ninety-eight percent of the comedocarcinoma diagnoses were made prior to 1997. During 1991-2000 comedo-DCIS accounted for 134/505 (26.5%) of all DCIS compared to 61/565 (10.8%) during 2001-2007 (p<0.0001). Patients with comedo-DCIS had a worse overall survival than other DCIS patients (p<0.040), but survival was similar for comedo-DCIS and invasive comedocarcinoma (p=0.62). Conclusion: Neoadjuvant chemotherapy plus trastuzumab can completely eradicate Her2-positive comedo-DCIS. Survival for comedo-DCIS is worse than for non-comedo DCIS and similar to invasive comedocarcinoma. Because of changes in synoptic reporting and current terminology in pathology reports, comedocarcinoma is no longer being documented and the diagnosis of comedo- DCIS has decreased. Additional studies are warranted to determine whether women with large breast lesions that show only comedo-DCIS on biopsy, should be considered candidates for neoadjuvant therapy to facilitate breast-conserving surgery.

Association of tamoxifen use and ovarian function in patients with invasive or pre-invasive breast cancer.

The impact of long-term tamoxifen therapy on ovarian function is not known. Understanding these effects will help reproductive-aged patients who desire future pregnancy make more informed decisions regarding their treatment. This is a retrospective cohort study in patients identified through the UCSF Cancer Registry and SPORE database. We enrolled women with a history of ductal carcinoma in situ (DCIS) or early stage invasive breast cancer who were premenopausal at diagnosis and did not receive chemotherapy. Menstrual histories were obtained through electronic and paper surveys. We compared the age of menopause onset and menstrual pattern changes between women who received tamoxifen (TAM) and those who did not receive tamoxifen (control). Neither group received chemotherapy. 250 subjects were included in this study (125 TAM, 125 control). Mean age of menopause onset was 51.0 for both the groups and was not associated with duration of tamoxifen use or the age at tamoxifen initiation. Menstrual pattern changes, including amenorrhea, were more frequent in the TAM group than control group (any change: 48% TAM vs. 15 % control, p < 0.001; amenorrhea: 22% TAM vs. 3% control, p < 0.001). Older age was associated with an increased risk of developing amenorrhea within 6 months of starting tamoxifen (HR 1.32, p < 0.001). Menstrual pattern changes are common in premenopausal women taking tamoxifen. Tamoxifen use in the absence of chemotherapy is not associated with an earlier age onset of menopause in patients with DCIS or invasive breast cancer and is unlikely to significantly accelerate ovarian aging.

Neoadjuvant chemotherapy (NC) in invasive breast cancer (IBC) subtypes: Outcomes according to pathological complete response (pCR) and proliferation index (PI) of residual tumor (RT).

e12027 Background: The outcomes of IBC pts who received NC could be different by subtypes. Methods: From 2000 to 2014 we treated 228 II-III stage IBC pts with NC.We recorded baseline features,type ...

Abstract P3-06-35: Association of estrogen receptor (ER) levels and prediction of antiproliferative effect of hormone therapy (HT) in lower ER-expressing tumors

Abstract Intro Accurate measurement of ER in early stage invasive breast cancer (EBC) is important to identify patients likely to benefit from HT. While immunohistochemistry (IHC) is the most common method to quantify ER, other methods can also accurately measure ER, such as RT-PCR. ER is one of the genes included in the RT-PCR based 21-gene Recurrence Score assay (Oncotype DX®, Genomic Health, Redwood City, CA) and is also reported separately as a single gene expression. Additionally, the association between ER expression by RT-PCR (ER-PCR) and tamoxifen benefit has been reported by Kim, et al (2011). A recent study reported that patients with ER levels &amp;lt;10% by IHC were largely negative by RT-PCR (Singh, et al; 2014) and that this has potential implications for which patients may be expected to benefit from HT. Robust measures of ER and the proliferative response may be useful in identifying patients likely to respond to HT. Aim The study aims are: (1) To correlate quantification of ER in EBC as assessed by Allred Score (AS) and ER as measured by RT-PCR in the 21-gene assay; (2) To describe changes in ER, Recurrence Score, and measures of proliferation after 2wks of an aromatase inhibitor (AI); (3) To perform exploratory analyses of factors associated with changes in proliferation. Methods 55 postmenopausal EBC patients with lower ER (AS 2-7) were treated with 2wks of an AI followed by wide excision. All patients had a 21-gene assay on a pre-and post-treatment (Tx) sample. Proliferation was measured by both Ki67 by IHC (in 45 patients) and by the proliferation gene group score (PGS) in the RT-PCR based 21-gene assay (in all patients). Proliferation response was defined by a 20% relative decrease in Ki67 or a decrease in PGS. Changes in proliferation were correlated with AS, ER-PCR and Recurrence Score result. Results The Table shows the correlation of AS with ER-PCR measured in the pre-Tx (r=0.83) samples. 94% of AS (2-3) patients and 56% of AS (4-5) were ER(-) by RT-PCR There was a significant change (pre to post) in the average Ki67 level (18% to 11%; p&amp;lt;0.001) and PGS but not Recurrence Score result. 37/45 patients showed a 20% decrease in Ki67 while only 32/55 had a decrease in PGS. Changes in Ki67 levels were greatest in AS 6/7 patients with a 76% relative decrease vs 21% in AS 2/3 patients. The range of PGS change was 1% increase in AS 2/3, 1% decrease in AS 4/5 and 14% decrease in AS 6/7 patients. Univariate predictors of decrease in Ki67 were AS of 5/6/7 (vs 2/3/4), Recurrence Score result, ER-PCR (continuous or binary), and PR-PCR. The same variables were predictors of PGS change. Pre-Tx ASER-PCR Status (Pre-Tx)NegativePositiveTotalAS 2-317 (94%)1(6%)18AS 4-59(56%)7(44%)6AS 6-70 (0%)21(100%)21Total262955 Conclusions • Results confirm earlier reports showing substantial disagreement in ER measured by IHC vs RT-PCR in patients with lower ER-expressing tumors • The clinical implications are that a substantial number of patients with low ER by IHC may have little to no benefit from HT • The 21-gene assay may be useful in selecting patients likely to benefit from HT • Further studies in larger cohorts are required to confirm these findings. Citation Format: J Michael Dixon, Arran Turnbull, Lorna Renshaw, Megan P Rothney, Cynthia A Loman, Laura Arthur, Jeremy S Thomas, Oliver Young, Juliette Murray, Linda Williams, Amy P Sing, David Cameron. Association of estrogen receptor (ER) levels and prediction of antiproliferative effect of hormone therapy (HT) in lower ER-expressing tumors [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-06-35.

Breast conservative therapy in Pakistani women: Prognostic factors for locoregional recurrence and overall survival.

Breast conservative therapy (BCT) is an established method of treating early stage invasive breast cancer. Survival after BCT in Pakistani population has not been reported. This study was carried out to report locoregional control and overall survival (OS) after BCT for invasive breast cancer and analyze prognostic factors in Pakistani population. Patients who received BCT between 1997 and 2009 were included in the study. Patients' follow-up, demographics, prognostic variables and treatment modalities were assessed. Data were analyzed for locoregional and distant relapse and estimated 10-year locoregional recurrence free survival (LRRFS) and OS was calculated using Kaplan Meier curves. To determine the significance of prognostic variables, univariate and multivariate analysis was performed. A total of 902 patients underwent BCT. Median age was 42 (17-82) years and the median follow-up was 51 (1.4-187) months. There were 484 (53.6) poorly differentiated and 194 (21.5) triple negative tumors. T3/T4 tumors were found in 128 (14.1) patients and 441 (44.8) patients had nodal involvement. Among adverse events, 58 (6.3) locoregional failures, 152 (16.8) distant failures and 155 (17.1) deaths were observed. Estimated 10 years LRRFS- was 88% while OS was 70%. On multivariate analysis, tumor size and nodal involvement were independent predictors of locoregional recurrence-free and OS. In addition, hormonal therapy significantly affected OS. BCT has acceptable long-term results in Pakistani women. Tumor size and nodal involvement are independent predictors of survival.

Abstract PR8: Socioeconomic determinants of the receipt of guideline-concordant breast cancer treatment

Abstract Background: Guidelines for the management of early stage invasive breast cancer include locoregional and systemic treatments that, on average, prolong disease-free and overall survival. Yet, a considerable proportion of women do not receive some or all of the guideline recommended breast cancer care. Disparities in the receipt of radiation therapy, chemotherapy, and endocrine therapy by patient and treatment facility characteristics may contribute to demographic differences in breast cancer survival. Methods: This population-based cohort study enrolled women aged 20 – 69 years, diagnosed with stage I, II, or IIIA breast cancer in the Seattle-Puget Sound area between 2004 and 2011, who were identified through the local Surveillance Epidemiology and End Results cancer registry. Concordance with National Comprehensive Cancer Network (NCCN) guideline recommendations and American Society of Clinical Oncology (ASCO)/NCCN Quality Measures (QMs) was assessed for 1,344 women using data collected from cancer registry records, pathology reports, and patient self-report from a telephone interview. Multivariable logistic regression was used to estimate the association between patient and facility characteristics, barriers and facilitators to care, and non-concordance with NCCN guidelines and QMs. Results: Compared to women with uninterrupted insurance coverage, women who did not have insurance at some point during their breast cancer treatment had a 3.5-fold (95% CI: 1.0-10.5) higher likelihood of non-concordance with NCCN guidelines for radiation therapy, and a 3.5-fold (95 % CI 1.2-10.5) higher likelihood of non-concordance with NCCN guidelines for chemotherapy. Low income was consistently associated with risk of non-concordance, with multivariate odds ratios of 2.3 (95% CI: 1.0-4.9) for radiation therapy guidelines, 4.6 (95% CI: 1.8-11.6) for chemotherapy guidelines, and 3.7 (95% CI: 1.4-9.7) for endocrine therapy guidelines associated with an annual family income of &amp;lt;$50,000 relative to that of ≥$90,000. We also observed consistent associations between financial insecurity and both NCCN guidelines and QMs and the amount of debt that a woman held at the time of breast cancer diagnosis was associated with a suggestion of an increased likelihood of non-concordance across all QMs. In addition, women who stated in the interview that they had problems talking to doctors or their staff (OR 2.7, 95% CI 1.1-6.4), women who stated that they did not have someone to go with them to appointments and drive them home (OR 3.3, 95% CI 1.4-7.9), and women who stated that they did not have someone to help them with daily chores and care for them if they were sick or tired (OR 2.2, 95% CI 1.0-4.7) were all at increased risk of non-concordance with NCCN chemotherapy guidelines. No clear pattern of non-concordance by education or treatment facility characteristics was observed. Conclusions: Economic factors were associated with non-receipt of most forms of recommended treatment. Our results and those of previous studies documenting socioeconomic disparities in the receipt of guideline recommended chemotherapy warrant further study of the root causes of these inequities, and of the effectiveness of interventions, such as patient navigation, designed to improve guideline concordance among uninsured, underinsured, and low-income women. This abstract is also presented as Poster A85. Citation Format: Jean A. McDougall, Noel S. Weiss, Kenneth J. Kopecky, Beti Thompson, Hannah M. Linden, Christopher I. Li. Socioeconomic determinants of the receipt of guideline-concordant breast cancer treatment. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr PR8. doi:10.1158/1538-7755.DISP13-PR8

The role of ultrasound-guided lymph node biopsy in axillary staging of invasive breast cancer in the post-ACOSOG Z0011 trial era.

Axillary status in invasive breast cancer, established by sentinel lymph node biopsy (SLNB) or ultrasound-guided lymph node biopsy, is an important prognostic indicator. The ACOSOG Z0011 trial showed that axillary dissection may be redundant in selected sentinel node-positive patients, raising questions on the applicability of these conclusions on ultrasound positive patients. The purpose of this study was to evaluate potential differences in patient and tumor characteristics and survival between axillary node positive patients after ultrasound (US group) or sentinel lymph node procedure (SN group). Patients diagnosed with invasive breast cancer at the Máxima Medical Center between January 2006 and December 2011 were studied. In total, 302 node-positive cases were included: 139 and 163 cases in the US and SN groups, respectively. Patients in the US group were older at diagnosis (p<0.001), more often had palpable nodes (p<0.001), mastectomy (p<0.001), larger tumors (p<0.001), higher tumor grade (p=0.001), lymphovascular invasion (p=0.035), a positive Her2Neu (p=0.006), and a negative hormonal receptor status (p=0.003). Also, they were more likely to have more lymph nodes with macrometastases (p<0.001), extranodal extension (p<0.001), and involvement of level-III-lymph node (p<0.001). Finally, they showed a worse disease-free survival [hazard ratio (HR)=2.71; 95% confidence interval (CI)=1.49-4.92] and overall survival (HR=2.67; 95% CI=1.48-4.84) than the SN group. These results suggest that ultrasound-positive patients have less favorable disease characteristics and a worse prognosis than SN-positive patients. Therefore, we conclude that omitting an ALND is as yet only applicable, as concluded in the Z0011, in patients with a positive SLNB.

“Choosing Wisely”: The American Society for Radiation Oncology’s Top 5 List

Purpose/Objective(s)To highlight five interventions that patients should question, as part of the Choosing Wisely campaign. This initiative, led by the American Board of Internal Medicine Foundation, fosters conversations between physicians and patients about treatments and tests that may be overused, unnecessary, or potentially harmful.Materials/MethodsPotential items were initially compiled using an online survey. They were then evaluated and refined by a workgroup representing the American Society of Radiation Oncology (ASTRO) Clinical Affairs and Quality, Health Policy, and Government Relations councils. Literature reviews were carried out to support the recommendation, narrative and references for each item. The final list of five items was selected by the ASTRO Board of Directors.ResultsASTRO’s five recommendations for the Choosing Wisely campaign are: (1) Don’t initiate whole breast radiation therapy as a part of breast conservation therapy in women age ≥50 with early stage invasive breast cancer without considering shorter treatment schedules. (2) Do not initiate management of low-risk prostate cancer without discussing active surveillance. (3) Do not routinely use extended fractionation schemes (>10 fractions) for palliation of bone metastases. (4) Don’t routinely recommend proton beam therapy for prostate cancer outside of a prospective clinical trial or registry. (5) Don't routinely use intensity modulated radiation therapy (IMRT) to deliver whole breast radiation therapy as part of breast conservation therapy.ConclusionsThe ASTRO list for the Choosing Wisely campaign highlights radiation oncology interventions that physicians should discuss with their patients before treatment is initiated. These five items provide opportunities for offering higher quality care. Purpose/Objective(s)To highlight five interventions that patients should question, as part of the Choosing Wisely campaign. This initiative, led by the American Board of Internal Medicine Foundation, fosters conversations between physicians and patients about treatments and tests that may be overused, unnecessary, or potentially harmful. To highlight five interventions that patients should question, as part of the Choosing Wisely campaign. This initiative, led by the American Board of Internal Medicine Foundation, fosters conversations between physicians and patients about treatments and tests that may be overused, unnecessary, or potentially harmful. Materials/MethodsPotential items were initially compiled using an online survey. They were then evaluated and refined by a workgroup representing the American Society of Radiation Oncology (ASTRO) Clinical Affairs and Quality, Health Policy, and Government Relations councils. Literature reviews were carried out to support the recommendation, narrative and references for each item. The final list of five items was selected by the ASTRO Board of Directors. Potential items were initially compiled using an online survey. They were then evaluated and refined by a workgroup representing the American Society of Radiation Oncology (ASTRO) Clinical Affairs and Quality, Health Policy, and Government Relations councils. Literature reviews were carried out to support the recommendation, narrative and references for each item. The final list of five items was selected by the ASTRO Board of Directors. ResultsASTRO’s five recommendations for the Choosing Wisely campaign are: (1) Don’t initiate whole breast radiation therapy as a part of breast conservation therapy in women age ≥50 with early stage invasive breast cancer without considering shorter treatment schedules. (2) Do not initiate management of low-risk prostate cancer without discussing active surveillance. (3) Do not routinely use extended fractionation schemes (>10 fractions) for palliation of bone metastases. (4) Don’t routinely recommend proton beam therapy for prostate cancer outside of a prospective clinical trial or registry. (5) Don't routinely use intensity modulated radiation therapy (IMRT) to deliver whole breast radiation therapy as part of breast conservation therapy. ASTRO’s five recommendations for the Choosing Wisely campaign are: (1) Don’t initiate whole breast radiation therapy as a part of breast conservation therapy in women age ≥50 with early stage invasive breast cancer without considering shorter treatment schedules. (2) Do not initiate management of low-risk prostate cancer without discussing active surveillance. (3) Do not routinely use extended fractionation schemes (>10 fractions) for palliation of bone metastases. (4) Don’t routinely recommend proton beam therapy for prostate cancer outside of a prospective clinical trial or registry. (5) Don't routinely use intensity modulated radiation therapy (IMRT) to deliver whole breast radiation therapy as part of breast conservation therapy. ConclusionsThe ASTRO list for the Choosing Wisely campaign highlights radiation oncology interventions that physicians should discuss with their patients before treatment is initiated. These five items provide opportunities for offering higher quality care. The ASTRO list for the Choosing Wisely campaign highlights radiation oncology interventions that physicians should discuss with their patients before treatment is initiated. These five items provide opportunities for offering higher quality care.

287P - A Laboratory Comparison of the 21-Gene Assay and Pam50-Ror

ABSTRACT Aim: The 21-gene Recurrence Score® assay is validated in patients (pts) with ER+ early stage invasive breast cancer (EBC) and predicts 10-yr distant recurrence risk and chemotherapy (CT) benefit. The Prosigna® assay (ROR) which uses 46 of the PAM50 genes, was validated in post-menopausal pts with ER+ EBC and is a prognostic assay only. Despite differences in platforms and methods used for development and validation, it is frequently believed that the assay results are interchangeable. We performed a study comparing results from the two assays obtained from the same tumor blocks. The first 40 samples showed a substantial disagreement in how the assays stratify risk. Methods: 70 sequential BC tumors from Marin Medical Laboratories with sufficient tumor material were selected to be tested with the standard 21-gene assay. Samples were sent to an independent lab where Prosigna ROR and intrinsic subtype was performed with the operators blinded to Recurrence Score results. The first 40 cases were stratified by Recurrence Score (20 low, 10 intermediate and 10 high) Descriptive statistics were used to compare results from the two assays. Results: Of the 40 initial pts evaluated, 7 were excluded: 3 for low RNA signal in the Prosigna assay and 4 were ER(-) by RT-PCR. Of the 33 remaining cases; 24 ductal, 7 lobular; 27 N(-); 6 N +. The Spearman rank correlation between Recurrence Score and ROR was 0.40 (95% CI 0.06–0.65). Risk group assignment (low/intermediate/high) between Recurrence Score and ROR was in agreement in 56% (15/27) of N(-). Prosigna classified 19 luminal A, 12 luminal B, 2 HER2 enriched and 0 basal. In both the luminal A and B groups there was a wide range of Recurrence Score results. Conclusions: Consistent with prior comparisons between the Oncotype DX and other genomic assays, there are substantial differences in the way pts are risk stratified and it cannot be assumed that the assay results are interchangeable. These results suggest that there is only a modest agreement between Recurrence Score results and ROR, with almost half of N(-), ER+ pts classified differently, including ∼30% of high ROR pts being classified as low risk by the Recurrence Score with expected minimal if any benefit from chemotherapy. Final data from 70 pts will be presented. Disclosure: M. Rothney, D. Cherbavaz: and C. Svedman: is an employee of Genomich Health International; C. Markopoulos: has an interest in relation with Genomic Health Inc: Speaker's Honoraria. All other authors have declared no conflicts of interest.