Early-stage Invasive Breast Cancer Research Articles

Recommendations from the EGAPP Working Group: does the use of Oncotype DX tumor gene expression profiling to guide treatment decisions improve outcomes in patients with breast cancer?

of The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group found insufficient evidence to recommend for or against the use of Oncotype DX testing to guide chemotherapy treatment decisions in women with hormone receptor-positive, lymph node-negative, or lymph node-positive early breast cancer who are receiving endocrine therapy. This recommendation statement updates a 2009 EGAPP statement on the use of gene expression profiling tests in breast cancer. Evidence of clinical validity for Oncotype DX was confirmed as adequate. With regard to clinical utility, although there was evidence from prospective retrospective studies that the Oncotype DX test predicts benefit from chemotherapy, and there was adequate evidence that the use of Oncotype DX gene expression profiling in clinical practice changes treatment decisions regarding chemotherapy, no direct evidence was found that the use of Oncotype DX testing leads to improved clinical outcomes. In women with early-stage invasive breast cancer, gene expression profiling is increasingly being used as an aid to estimate the likely benefit from chemotherapy treatment. In a previous recommendation statement, the EGAPP Working Group (EWG) found adequate evidence for clinical validity of some gene expression profiling tests in predicting distant disease recurrence in women with early-stage, hormone receptor-positive, lymph-node-negative breast cancer who are treated with tamoxifen, but insufficient evidence that use of these tests for decisions about chemotherapy treatment has clinical utility. The current recommendation statement updates these findings for Oncotype DX and extends them to the population of women with lymph node-positive disease, using evidence from recent systematic reviews and other sources. The previous recommendation statement found that evidence was inadequate to enable quantitative determination of the analytic validity of Oncotype DX. Analytic validity was not reconsidered in the updated recommendation statement because there remains no gold-standard test for comparison. The EWG found that new evidence published since the original evidence review supports the clinical validity of Oncotype DX in predicting risk of distant metastases in women with hormone receptor-positive, early-stage breast cancer that is either node-negative or node-positive. No direct evidence was found that use of Oncotype DX tumor gene expression profiling to guide treatment decisions improves clinical outcomes in women with early breast cancer. There is indirect evidence, from prospective retrospective studies on archived tissue samples from randomized controlled trials, that the Oncotype DX test can predict benefit from chemotherapy. Large, prospective, randomized, controlled trials currently in progress may provide evidence of clinical utility. Until definitive evidence for clinical utility is available, clinicians must decide on a case-by-case basis whether to offer the test to patients. Although Oncotype DX testing has been reported, on the basis of economic modeling studies, to be cost-effective in several different health-care systems and to save costs in the US health-care setting, studies were based on assumptions regarding the clinical utility of the test that require confirmation by clinical trial results.Genet Med 18 8, 770-779.

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

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.

Not Performing a Sentinel Node Biopsy for Older Patients With Early-Stage Invasive Breast Cancer.

Not Performing a Sentinel Node Biopsy for Older Patients With Early-Stage Invasive Breast Cancer.

KPNA2 is a nuclear export protein that contributes to aberrant localisation of key proteins and poor prognosis of breast cancer.

Background:It is recognised that modulations of the nuclear import of macromolecules have a role in changing cellular phenotypes and carcinogenesis. We and others have noticed that aberrant subcellular localisation of DNA damage response (DDR) proteins in breast cancer (BC) is associated with loss-of-function phenotype. This study aims to investigate the biological and clinical significance of the nucleocytoplasmic transport protein karyopherin α-2 (KPNA2), and its role in controlling DDR proteins subcellular localisation in BC.Methods:A large (n=1494) and well-characterised series of early-stage invasive BC with a long-term follow-up was assessed for KPNA2 protein by using immunohistochemistry.Results:KPNA2 expression was associated with the subcellular localisation of key DDR proteins that showed cytoplasmic expression including BRCA1, RAD51, SMC6L1, γH2AX, BARD1, UBC9, PIAS1 and CHK1. High level of KPNA2 was associated not only with cytoplasmic localisation of these proteins but also with their low/negative nuclear expression. Positive KPNA2 expression was associated with negative oestrogen receptor and triple-negative phenotype. Survival analysis showed that KPNA2 was associated with poor outcome (P<0.0001), but this effect was not independent of other prognostic variables.Conclusions:This study provides further evidence for the complexity of DDR mechanism in BC, and that KNPA2 has a role in the aberrant subcellular localisation of DDR proteins with subsequent impaired function.

Markers of progression in early-stage invasive breast cancer: a predictive immunohistochemical panel algorithm for distant recurrence risk stratification.

Accurate distant metastasis (DM) prediction is critical for risk stratification and effective treatment decisions in breast cancer (BC). Many prognostic markers/models based on tissue marker studies are continually emerging using conventional statistical approaches analysing complex/dimensional data association with DM/poor prognosis. However, few of them have fulfilled satisfactory evidences for clinical application. This study aimed at building DM risk assessment algorithm for BC patients. A well-characterised series of early invasive primary operable BC (n = 1902), with immunohistochemical expression of a panel of biomarkers (n = 31) formed the material of this study. Decision tree algorithm was computed using WEKA software, utilising quantitative biomarkers' expression and the absence/presence of distant metastases. Fifteen biomarkers were significantly associated with DM, with six temporal subgroups characterised based on time to development of DM ranging from <1 to >15 years of follow-up. Of these 15 biomarkers, 10 had a significant expression pattern where Ki67LI, HER2, p53, N-cadherin, P-cadherin, PIK3CA and TOMM34 showed significantly higher expressions with earlier development of DM. In contrast, higher expressions of ER, PR and BCL2 were associated with delayed occurrence of DM. DM prediction algorithm was built utilising cases informative for the 15 significant markers. Four risk groups of patients were characterised. Three markers p53, HER2 and BCL2 predicted the probability of DM, based on software-generated cut-offs, with a precision rate of 81.1 % for positive predictive value and 77.3 %, for the negative predictive value. This algorithm reiterates the reported prognostic values of these three markers and underscores their central biological role in BC progression. Further independent validation of this pruned panel of biomarkers is therefore warranted.

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.

Abstract OT3-2-03: Prospective observational study of clinical outcomes for the NanoString® technologies Prosigna™ test by the West German Study Group

Abstract Background: Current diagnostic tools for breast cancer (BC), including screening, diagnostic breast imaging and biopsy, do not provide information about subtype classification. However, the subtype classification is crucial for the assessment of the recurrence risk and for the choice of optimal adjuvant treatment. A vast amount of data from recent research, clinical trials, and peer reviewed publications support the value of intrinsic subtyping based on gene expression analyses to assess prognosis and treatment options for patients with early BC. Trial design: The multicenter (n=8), prospective study examines whether the Prosigna™ test influences physician and patient adjuvant treatment selection over and above currently used prognostic factors. It also examines the impact of the test results on patients’ reported outcomes including their decisional conflict status, anxiety levels, and functional status. Prosigna™ is a standardized test measuring the expression levels of 50 classifier genes in formalin-fixed, paraffin-embedded tissue samples and provides a subtype classification based on the fundamental biology of individual patient’s tumor (intrinsic subtyping), as well as a prognostic score (risk of recurrence (ROR) score) that predicts the probability of cancer recurrence over 10 years. Eligibility criteria: Postmenopausal women with resected N0, estrogen-receptor-positive (ER) (by immunohistochemistry (IHC); &amp;gt;1% of stained tumor cells is considered positive), HER2-negative (IHC and/or in-situ fluorescence hybridization by local laboratory), early-stage invasive BC (T1-T2, pN0 (i+/mol+), M0). Patients must be able to give consent and must be eligible for treatment with adjuvant chemotherapy (Ctx) (ECOG performance status ≤1). Patients with non-invasive (e.g. Paget’s disease, DCIS), ER-negative or HER2-positive BC must not be included. Metastatic disease and contraindications for adjuvant Ctx (age, ECOG &amp;gt;1, significant comorbidities) are exclusion criteria. Patients unable to complete patient reported outcome surveys will be excluded. Specific aims: Primary endpoint is the proportion of patients whose choice of treatment is changed as a result of receiving the Prosigna™ result. Secondary endpoints include the proportion of patients whose choice of treatment is changed stratified by ROR groups (low, intermediate, high) and who have cancer recurrence risk proximal to the cutoff points between risk strata (± 5% from cutoff point). Investigators’ confidence in treatment recommendations before/after Prosigna™ results and change in patients’ decisional conflict status, anxiety levels, and functional status, stratified by cancer recurrence risk strata, will be investigated. Rate and severity of treatment-related adverse events stratified by whether patient received adjuvant Ctx and agreement in molecular subtyping between Prosigna™ and local IHC will be evaluated. Statistical methods: Sample size of 200 produces a one-sided 95% lower-limit CI with a distance from the sample proportion to the lower limit that is equal to 0.05 when the sample proportion is 0.25. Present and target accrual: A total of 200 patients will be included, current accrual is n=111 as of 3rd June 2014. Citation Format: Rachel Wuerstlein, Karl Sotlar, Burkhard Otremba, Oleg Gluz, Enrico Pelz, Daniel Hofmann, Ronald E Kates, Isabelle Witzel, Christian Schindlbeck, Wolfgang Janni, Christian Schem, Hans Tesch, Nadia Harbeck. Prospective observational study of clinical outcomes for the NanoString® technologies Prosigna™ test by the West German Study Group [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 OT3-2-03.

Is mastectomy undertreatment for low-risk breast cancers eligible for breast-conserving therapy?

Biomarkers are routinely used to predict responses to systemic therapies, but their utility for predicting responses to local therapy for breast cancer is not known. This study determined whether biomarkers could predict responses to breast-conserving therapy (BCT) and mastectomy. A review of the Surveillance, Epidemiology, and End Results database identified women diagnosed with early-stage invasive ductal breast cancer and treated with BCT or mastectomy from 1998 to 2008. The estrogen receptor (ER) status and the histologic grade were used to construct 3 biomarker profiles: low risk (ER-positive, low/intermediate grade), intermediate risk (ER-positive, high grade), and high risk (ER-negative, any grade). The primary measured outcome was disease-specific survival (DSS). BCT and mastectomy were performed in 114,486 patients (59.2%) and 79,035 patients (40.8%), respectively. There were 122,420 low-risk patients (63.3%), 34,341 intermediate-risk patients (17.7%), and 36,760 high-risk patients (19.0%). Multivariate analyses were performed separately for patients with low-, intermediate-, and high-risk tumors. The adjusted hazard ratios for DSS for patients who underwent mastectomy versus BCT for low-, intermediate-, and high-risk tumors were 1.66 (95% confidence interval [CI], 1.54-1.79; P < .001), 1.40 (95% CI, 1.29-1.53; P < .001), and 1.27 (95% CI, 1.19-1.35; P < .001), respectively. Patients with ER-positive, low-grade breast cancers who underwent mastectomy had a 66% increase in disease-specific mortality versus those who underwent BCT. Biomarker profiles defined by the ER status and grade may improve the selection of local therapy for breast cancer.

Weight and weight change following breast cancer: evidence from a prospective, population-based, breast cancer cohort study.

BackgroundWhile weight gain following breast cancer is considered common, results supporting these findings are dated. This work describes changes in body weight following breast cancer over 72 months, compares weight with normative data and explores whether weight changes over time are associated with personal, diagnostic, treatment or behavioral characteristics.MethodsA population-based sample of 287 Australian women diagnosed with early-stage invasive breast cancer was assessed prospectively at six, 12, 18 and 72 months post-surgery. Weight was clinically measured and linear mixed models were used to explore associations between weight and participant characteristics (collected via self-administered questionnaire). Those with BMI changes of one or more units were considered to have experienced clinically significant changes in weight.ResultsMore than half (57%) of participants were overweight or obese at 6 months post-surgery, and by 72 months post-surgery 68% of women were overweight or obese. Among those who gained more weight than age-matched norms, clinically significant weight gain between 6 and 18 months and 6 and 72 months post-surgery was observed in 24% and 39% of participants, respectively (median [range] weight gain: 3.9 kg [2.0-11.3 kg] and 5.2 kg [0.6-28.7], respectively). Clinically-significant weight losses were observed in up to 24% of the sample (median [range] weight loss between 6 and 72 months post-surgery: −6.4 kg [−1.9--24.6 kg]). More extensive lymph node removal, being treated on the non-dominant side, receiving radiation therapy and lower physical activity levels at 6 months was associated with higher body weights post-breast cancer (group differences >3 kg; all p < 0.05).ConclusionsWhile average weight gain among breast cancer survivors in the long-term is small, subgroups of women experience greater gains linked with adverse health and above that experienced by age-matched counterparts. Weight change post-breast cancer is a contemporary public health issue and the integration of healthy weight education and support into standard breast cancer care has potential to significantly improve the length and quality of cancer survivorship.

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.

Optimal Margin Width in Breast Conservation Therapy: a Review of the Current Guidelines and Literature

Randomized trials have clearly established breast conservation therapy (BCT) as appropriate treatment for early-stage invasive breast cancer. Current evidence shows that positive margins confer a greater than twofold risk of ipsilateral breast tumor recurrence. Thus, patients who have positive margins after BCT warrant re-excision. With regard to negative margins, however, the optimal negative margin width remains unclear. This article reviews the recent guidelines set forth by the Society of Surgical Oncology and the American Society of Radiation Oncology regarding the margin width in stage I and II invasive breast cancer. We also discuss the controversies related to implementation of these guidelines.

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

Choosing Wisely: The American Society for Radiation Oncology’s Top 5 list

PurposeTo highlight 5 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. Methods and materialsPotential items were initially compiled using an online survey. They were then evaluated and refined by a work group representing the American Society for Radiation Oncology (ASTRO) Clinical Affairs and Quality, Health Policy, and Government Relations Councils. Literature reviews were carried out to support the recommendation and narrative, as well as to provide references for each item. A final list of 5 items was then selected by the ASTRO Board of Directors. ResultsASTRO’s 5 recommendations for the Choosing Wisely campaign are the following: (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) don’t initiate management of low-risk prostate cancer without discussing active surveillance; (3) don’t 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; and (5) don't routinely use intensity modulated radiation therapy 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 should be discussed between physicians and patients before treatment is initiated. These 5 items provide opportunities to offer higher quality and less costly care.

“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.

Our panel of experts highlight the most important research articles across the spectrum of topics relevant to the field of breast cancer management

Breast Cancer ManagementVol. 3, No. 5 Journal WatchFree AccessJournal WatchElizabeth A Mittendorf & Lawrence J SolinElizabeth A MittendorfDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Pressler St, Unit 1434, Houston, TX 77030, USASearch for more papers by this author & Lawrence J SolinDepartment of Radiation Oncology, Albert Einstein Healthcare Network, Philadelphia, PA, USASearch for more papers by this authorPublished Online:27 Oct 2014https://doi.org/10.2217/bmt.14.43AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInRedditEmail Moran MS, Schnitt SJ, Giuliano AE et al. Society of Surgical Oncology–American Society for Radiation Oncology consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in stages I and II invasive breast cancer. This article was copublished by The Society of Surgical Oncology: Ann. Surg. Oncol. 21(3), 704–716 (2014); The American Society for Radiation Oncology: Int. J. Radiat. Oncol. Biol. Phys. 88(3), 553–564 (2014); American Society of Clinical Oncology: J. Clin. Oncol. 32(14), 1507–1515 (2014).The definition of an adequate margin for breast-conserving surgery has been debated. The recently published consensus guidelines support using “no ink on tumor” as the standard in stage I and II breast cancer patients treated with whole-breast irradiation. This recommendation is based on a meta-analysis of studies evaluating the impact of margin width on ipsilateral breast tumor recurrence (IBTR) [1]. Positive margins, defined as ink on invasive carcinoma or ductal carcinoma in situ, was associated with a twofold increased IBTR risk compared with negative margins. More widely clear margins did not reduce IBTR. The low IBTR rate (5.3% median prevalence at 79.2-month median follow-up) reported in the meta-analysis reflects improvements in imaging and pathologic assessment, as well increased understanding of tumor biology and improvements in systemic therapy and radiation delivery. In the contemporary era of multidisciplinary care of breast cancer patients, “no ink on tumor” will be adequate in most cases and implementation of these guidelines will decrease re-excision rates, thereby reducing variability and costs of care as well as improving cosmetic outcomes.– Written by EA MittendorfRueth NM, Lin HY, Bedrosian I et al. Underuse of trimodality treatment affects survival for patients with inflammatory breast cancer: an analysis of treatment and survival trends from the National Cancer Database. J. Clin. Oncol. 32, 2018–2024 (2014).Although uncommon, inflammatory breast cancer is a rapidly progressive and often lethal form of breast cancer. Optimal management typically includes trimodality (multimodality) treatment, beginning with neoadjuvant chemotherapy, followed by local–regional treatment, and then hormonal therapy (for hormone receptor-positive tumors).Rueth et al. report an analysis of 10,197 patients with inflammatory breast cancer using the National Cancer Data Base. While most patients (67%) received trimodality treatment, a substantial fraction of patients did not, most commonly receiving surgery plus chemotherapy but without radiation treatment.Overall survival rates were highest for those patients who had received trimodality treatment in comparison to other groups. After trimodality treatment, overall survival rates were 55.4% and 37.3% at 5 and 10 years, respectively. On multivariable analysis, trimodality treatment remained a statistically significant variable. These results demonstrate that patients with inflammatory breast cancer receiving trimodality treatment can have meaningful long-term survival.– Written by LJ SolinFinancial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.References1 Houssami N, Macaskill P, Marinovich ML, Morrow M. The association of surgical margins and local recurrence in women with early-stage invasive breast cancer treated with breast-conserving therapy: a meta-analysis. Ann. Surg. Oncol. 21(3), 717–730 (2014).Crossref, Medline, Google ScholarFiguresReferencesRelatedDetails Vol. 3, No. 5 Follow us on social media for the latest updates Metrics Downloaded 141 times History Published online 27 October 2014 Published in print September 2014 Information© Future Medicine LtdFinancial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.PDF download

Frontiers in radiotherapy for early-stage invasive breast cancer.

The development of breast-conserving treatment for early-stage breast cancer is one of the most important success stories in radiation oncology in the latter half of the twentieth century. Lumpectomy followed by radiotherapy provides an appealing alternative to mastectomy for many women. In recent years, there has been a shift in clinical investigational focus toward refinements in the methods of delivering adjuvant radiotherapy that provide shorter, more convenient schedules of external-beam radiotherapy and interstitial treatment. Expedited courses of whole-breast treatment have been demonstrated to be equivalent to traditional lengthier courses in terms of tumor control and cosmetic outcome and to provide an opportunity for cost efficiencies.

Sorting out the survival impact of radiation therapy in early-stage invasive breast cancer.

Radiation plays a major role in the management of early-stage breast cancer. While its impact on local–regional control is clearly documented with both clinically and statistically significant gains, the impact of radiation on overall and disease-free survival in early-stage disease remains a matter of controversy and debate.1–4 There are two major areas where the impact of radiation therapy on overall and disease-free survival has been extensively evaluated: 1. radiation to the whole breast following breast-conserving surgery (BCS + RT) and 2. comprehensive irradiation to the chest wall/breast and regional lymphatics after definitive surgery. In this commentary, we will review the evidence and controversies in these two major areas.1–3

A pilot laboratory study comparing the 21-gene assay and PAM50-ROR.

11003 Background: The Oncotype DX 21-gene Recurrence Score assay was developed in endocrine-treated patients (pts) and validated as a predictor of 10-yr distant recurrence risk and chemotherapy benefit in ER+ early-stage invasive breast cancer. The Prosigna assay (ROR) which uses 46 of the PAM50 genes, was validated on centrally processed samples as a prognostic assay only in endocrine treated, post-menopausal pts. To date no direct comparison data on paired samples from the same patients for these two assays has been reported and yet it’s frequently believed that these assays are interchangeable. We performed a pilot study comparing test results from the two assays obtained from the same tumor blocks. Methods: Sequential breast cancer tumors from Marin Medical Laboratories with sufficient tumor material were tested with the standard 21-gene Recurrence Score assay. 40 cases stratified by the Recurrence Score (20 low, 10 intermediate and 10 high) were sent to an independent laboratory where the Prosigna assay for ROR and intrinsic subtype was performed with the operators blinded to the Recurrence Score results. Descriptive statistics were calculated for the results obtained from the two assays. Results: Of the 40 pts, 3 were excluded due to low RNA signal in the Prosigna assay and 4 were ER(-) by RT-PCR. Of the 33 remaining cases, 24 were ductal, 7 lobular and 2 other; 27 were N- and 6 were 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(-) pts. Prosigna classified 19 as luminal A, 12 as luminal B, 2 as HER2 enriched and 0 as basal. In both the luminal A and B groups there was a wide range of Recurrence Score results. Conclusions: Consistent with other comparisons between expression-based assays, it should not be assumed that these assays are interchangeable. While additional data from a larger independent analysis is needed, this pilot suggests that there is only a modest agreement between the Recurrence Score and ROR, with almost half of N(-), ER+ pts classified differently.