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Aim: Identification of molecular determinants predicting late recurrence (>5 yrs) in stage I and II breast cancer has become clinically important in light of data demonstrating a benefit for 10 yrs of tamoxifen administration. Since the 21-gene Recurrence Score (RS) is commonly utilized in early stage BC, we wished to determine its utility in predicting distant recurrences beyond 5 yrs as a function of quantitative ER expression. Methods: The 21-gene RS was assessed in 1065 chemo and tam-treated, ER + , node-positive pts from NSABP B-28 and 668 tam-treated, ER + , node-negative pts from NSABP B-14. Cox PH models, KM estimates and log rank statistics were used to assess the association of the RS with risk of DR by quantitative ER expression, using the 21-gene assay, in pts event-free after 5 yrs. We established an ER cut-point (high vs low) in B-28, and tested the cut-point in B-14, formally evaluating the interaction of RS and ER. Results: Median follow-up was 11.2 yrs (B-28) and 14.5 yrs (B-14). 832 B-28 pts and 564 B-14 pts were DR-free after 5 yrs. A reference normalized ER cut-point of 9.1 CT was established in B-28 based on the association of the RS with DR after 5 yrs. Of the event-free pts at 5 yrs, 68% in B-28 and 88% in B-14 had ER > 9.1. In B-28 the RS result was strongly associated with DR after 5 yrs in the higher ER expressing pts (log rank P = 0.001), but not in the lower ER expressing pts (log rank P = 0.87). It was confirmed in the B-14 data that RS was associated with DR after 5 yrs in higher ER pts (Table) but not in the lower ER pts (interaction P = 0.03). The association of RS risk groups within clinicopathologic subgroups for the higher ER patients still at risk at 5 years will also be presented. Table 177P . DR Risk after 5 yrs in B-14 by RS Risk Group for pts with ER > 9.1 C T % DR KM estimate (95% CI) RS Risk Group N(%) pts 5 to 10 yrs (%) 5 to 15 yrs % Low 289 (58%) 4.7 (2.8 – 8.0) 6.8 (4.4 – 10.6) Intermediate 111 (22%) 4.1 (1.6 – 10.6) 11.2 (6.2 – 19.9) High 97 (20%) 12.6 (7.4 – 21.2) 16.4 (10.2 – 25.7) Log rank P = 0.01 Conclusions: For late recurrences (beyond 5 yrs), the RS is strongly prognostic in pts with higher quantitative ER expression (>9.1). The findings suggest that extending tamoxifen beyond 5 yrs may be most beneficial in pts with high (and intermediate) RS with higher quantitative ER expression and of limited benefit in pts with a low RS (>50% of population under study). Disclosure: F. Baehner, S. Butler, F. Jamshidian and A. Sing have decalred: I am an employee of Genomic Health, Inc. I receive a salary and company stock. S. Shak: I am an employee of Genomic Health, Inc and I serve in a leadership position. I receive a salary and I have company stock.All other authors have declared no conflicts of interest.

Aim: For early stage HR + , HER2– BC pts with intermediate risk by clinical/pathologic criteria, treatment decisions should be based on sensitivity to endocrine therapy, risk of recurrence, and predicted benefit from CT. The ESMO guidelines highlight that multigene assays (MGA) may be used in these cases (Ann Oncol. 2013;suppl6:vi7-23). The MAGIC survey evaluated criteria considered for CT decisions and simulated CT recommendations for pts with different characteristics. We present CT recommendations for intermediate-risk BC pts based on characteristics of respondents. Methods: The online survey was completed by physicians working in multidisciplinary BC teams, having ≥5 year experience. A conjoint analysis was used to model CT recommendations for simulated pts. Results: Overall recommendations (n = 911, 52 countries) showed that BC pt profiles associated with a request for more information tended to have an intermediate/high age (>50 yr), intermediate/small tumor size, grade 1/2, low ER/intermediate Ki67 expression, and node-negative status. The table summarizes CT recommendations for 4 selected intermediate-risk BC pts. On average, CT was recommended for the 4 pt profiles by 29%, 42%, 31%, and 44% of responders. CT recommendation varied greatly among different countries for each pt profile. Physicians who always use international guidelines tended to prescribe CT more often, while those who use MGA, as expected, recommended CT less frequently for each pt profile. More-experienced physicians (ie, those who prescribe CT personally or who treat >200 pts/year) showed a slight trend to fewer CT recommendations. Conclusions: There is high variation in CT recommendations for intermediate-risk BC pts, primarily according to country of residence. There is a need for more broadly available tools, such as MGA, to help make more-informed treatment decisions in this pt population. Table: 261PD . Selected MAGIC survey respondent groups recommending CT for selected patient profiles Patient profile 1 ( age 35–50 , tumor size 1–2 cm, tumor grade 2, high ER, high PR , 14%–20% Ki67, node negative) Patient profile 2 ( age 35–50 , tumor size 1–2 cm, tumor grade 2, high ER, low PR , 14%–20% Ki67, node negative) Patient profile 3 ( age 51–70 , tumor size 2.1–3 cm, tumor grade 2, high ER, high PR , 14%–20% Ki67, node negative) Patient profile 4 ( age 51–70 , tumor size 2.1–3 cm, tumor grade 2, high ER, low PR , 14%–20% Ki67, node negative) All physicians (excluding pathologists, n = 877) 29% 42% 31% 44% All physicians – range between countries with >30 respondents 15%–41% 33%–50% 14%–48% 28%–56% Physicians personally prescribing CT (n = 610)/not prescribing CT (n = 267) 27%/31% 42%/44% 30%/34% 43%/46% Physicians treating 1–50 pts per year (n = 310)/ > 200 pts per year (n = 86) 32%/26% 45%/38% 36%/26% 49%/38% Physicians always (n = 482)/often (n = 377) using international guidelines 31%/25% 45%/39% 34%/27% 47%/40% Physicians using (n = 487)/not using (n = 390) MGA 26%/31% 39%/46% 29%/34% 41%/48% Medical oncologist (n = 485)/surgeons or gynecologists (n = 324)/radiation oncologists (n = 38) 27%/30%/32% 42%/42%/46% 30%/32%/33% 45%/44%/46% Physicians working in an academic hospital (n = 540)/community-based or private hospital (n = 240)/office-based or private practice (n = 77) 29%/27%/34% 42%/43%/45% 31%/31%/36% 43%/47%/47% ER, estrogen receptor; PR, progesterone receptor Disclosure: M. De Laurentiis: Advisory board: Genomic Health; M. Aapro: Advisory board: Genomic Health Corporate-sponsored research: Genomic Health; C. Markopoulos: Other substantive relationships: Genomic Health – Speaker's Honoraria; T. Mamounas: Advisory board: Genomic Health Inc. Other substantive relationships: Speaker's Bureau: Genomic Health Inc.; R. Rouzier: Advisory board: consultant for Genomic Health; C. Thomssen: Advisory board: Genomic Health Other substantive relationships: Speaker for Genomic Health; D. Rea: Advisory board: Genomic Health; B. Linderholm: Board of directors: Steering Committee for the BIG/EORTC/NABCG Male breast cancer project; V. Smit: Advisory board: Genomic Health Inc.; C. Svedman: Other substantive relationships: I am an employee of Genomic Health working in the medical department.All other authors have declared no conflicts of interest.

Aim: The MAGIC survey aimed to identify how physicians use the most common traditional parameters and histopathology markers in clinical treatment decisions in early stage HR + , HER2– breast cancer. The data presented here describe how physicians use tumor size, grade, nodal status, estrogen receptor (ER), progesterone receptor (PR), and Ki67 expression, and age for CT recommendations. Methods: The online MAGIC survey was available to physicians working in multidisciplinary breast cancer teams (≥5 years' experience). The survey evaluated respondent demographics, criteria considered for CT decisions, and treatment recommendations in a wide variety of patient cases and captured how physicians use traditional parameters for making CT recommendations. Results: Between August 2013 and January 2014, 911 respondents (52 countries) completed the survey. The results for key parameters are presented in the table. There was substantial heterogeneity in how all parameters were considered for decisions about CT, with a majority of respondents reaching agreement to strongly consider CT only in patients with Grade 3 tumors (70.1%), tumors larger than 3 cm (63.7%), and in patients with 2 or more positive nodes (63.1%). A majority would strongly consider CT in patients with low ER and high Ki67 expression but there was no consensus on the definition of low ER expression ( 20% [33.9%], > 30% [31.9%]). Conclusions: The results reveal substantial differences in how physicians use traditional prognostic parameters for CT decisions. The data highlight the need for implementation of additional criteria or biomarkers that are predictive of CT benefit and can help physicians and patients make more informed treatment decisions. Is there a specific tumor size above which you would strongly consider CT? > 1 cm 13.8% > 2 cm 35.5% > 3 cm 14.4% > 4 cm 4.7% > 5 cm 9.4% Not considered 22.2% Is there a specific tumor grade above which you would strongly consider CT? Grade 1 or above 0.6% Grade 2 or above 20.9% Grade 3 or above 70.1% Not considered 8.4% Would you be inclined to give CT to most patients with low expression of ER? Yes 83.4% No 8.4% Not considered 8.2% Would you be inclined to give CT to patients with low PR? Yes 41.9% No 21.3% Not considered 36.9% What percentage of ER+ cells would you consider low and would make you strongly consider CT? 26.2% 46.8% 20.0% Not considered 7.1% At which Ki67 percentage would you strongly consider giving CT? ≥ 14% 27.2% > 20% 33.9% > 30% 31.9% Not considered 7.1% What number of positive nodes would make you strongly consider CT? Node negative 3.6% 1 (including isolated tumor cells or nodal micrometastases) 38.6% 2 20.9% 3 10.8% 4 or more 21.0% Not considered 5.0% Is there an age above which you would strongly consider not giving adjuvant CT? > 50 years 1.4% > 60 years 0.7% > 70 years 16.8% > 80 years 48.4% Age is not considered 32.8% Disclosure: M. Aapro: Advisory board: Genomic Health Corporate-sponsored research: Genomic Health; C. Markopoulos: Other substantive relationships: Genomic Health – Speaker's Honoraria; T. Mamounas: Advisory board: Genomic Health Inc. Other substantive relationships: Speaker's Bureau: Genomic Health Inc.; R. Rouzier: Advisory board: consultant for Genomic Health; C. Thomssen: Advisory board: Genomic Health Speaker for Genomic Health (under other substantive relationships); D. Rea: Advisory board: Genomic Health; B. Linderholm: Board of directors: Steering Committee for the BIG/EORTC/NABCG Male breast cancer project; V. Smit: Advisory board for Genomic Health Inc.; C. Svedman: Other substantive relationships: I am an employee of Genomic Health working in the medical department; M. De Laurentiis: Advisory board: Genomic Health. All other authors have declared no conflicts of interest.