Nicky Liebermann

Screening and Diagnosis of Gestational Diabetes Mellitus:: Critical appraisal of the new International Association of Diabetes in Pregnancy Study Group recommendations on a national level

OBJECTIVE To study the implications of implementing the International Association of Diabetes in Pregnancy Study Group (IADPSG) recommendations for screening and diagnosis of gestational diabetes mellitus (GDM) in Israel and explore alternative methods for identifying women at risk for adverse pregnancy outcomes. RESEARCH DESIGN AND METHODS We analyzed data of the Israeli Hyperglycemia and Adverse Pregnancy Outcomes study participants (N = 3,345). Adverse outcome rates were calculated and compared for women who were positive according to 1) IADPSG criteria, 2) IADPSG criteria with risk stratification, or 3) screening with BMI or fasting plasma glucose (FPG). RESULTS Adopting IADPSG recommendations would increase GDM diagnosis by ∼50%. One-third of IADPSG-positive women were at low risk for adverse outcomes and could be managed less intensively. FPG ≥89 mg/dL or BMI ≥33.5 kg/m2 at 28–32 weeks of gestation detected proportions of adverse outcomes similar to IADPSG criteria. CONCLUSIONS Implementing IADPSG recommendations will substantially increase GDM diagnosis. Risk stratification in IADPSG-positive women may reduce over-treatment. Screening with FPG or BMI may be a practical alternative.

Clinical outcomes in patients with node-negative breast cancer treated based on the recurrence score results: evidence from a large prospectively designed registry

The 21-gene Recurrence Score® (RS) assay is a validated prognostic/predictive tool in ER + early-stage breast cancer. However, clinical outcome data from prospective studies in RS ≥ 11 patients are lacking, as are relevant real-life clinical practice data. In this retrospective analysis of a prospectively designed registry, we evaluated treatments/clinical outcomes in patients undergoing RS-testing through Clalit Health Services. The analysis included N0 ER + HER2-negative breast cancer patients who were RS-tested from 1/2006 through 12/2010. Medical records were reviewed to verify treatments/recurrences/survival. The cohort included 1801 patients (median follow-up, 6.2 years). Median age was 60 years, 50.4% were grade 2 and 81.1% had invasive ductal carcinoma; 48.9% had RS < 18, 40.7% RS 18–30, and 10.4% RS ≥ 31, with chemotherapy use of 1.4, 23.7, and 87.2%, respectively. The 5-year Kaplan–Meier estimates for distant recurrence were 0.8, 3.0, and 8.6%, for patients with RS < 18, RS 18–30 and RS ≥ 31, respectively; the corresponding 5-year Kaplan–Meier estimates for breast cancer death were 0.0, 0.9, and 6.2%. Chemotherapy-untreated patients with RS < 11 (n = 304) and 11–25 (n = 1037) (TAILORx categorization) had 5-year Kaplan–Meier estimates for distant recurrence risk/breast cancer death of 1.0%/0.0% and 1.3%/0.4%, respectively. Our results extend those of the prospective TAILORx trial: the 5-year Kaplan–Meier estimates for distant recurrence and breast cancer death rate for the RS < 18 patients were very low supporting the use of endocrine therapy alone. Furthermore, in chemotherapy-untreated patients with RS 11–25 (where TAILORx patients were randomized to chemoendocrine or endocrine therapy alone), 5-year distant recurrence rates were also very low, suggesting that chemotherapy would not have conferred clinically meaningful benefit.Genetic testing: Diagnostic shows which node-negative patients need chemoPatients with early breast cancer that hasn’t spread to lymph nodes can likely forgo chemotherapy if they score under 25 on Oncotype DX. That’s the finding of a retrospective analysis led by Salomon Stemmer from Rabin Medical Center in Petah Tikvah, Israel, that looked at 1801 women with node-negative, ER-positive, HER2-negative disease who received the diagnostic test, which measures the expression levels of 21 genes within tumor cells. Rates of disease recurrence and death were low for patients who received only anti-hormone treatment and had low-to-intermediate Oncotype DX results, suggesting no need for additional chemotherapy (which carries an appreciable risk of toxicity). Previously, a prospective US study called TAILORx established that women with scores under 11 could be spared chemotherapy. The Israeli trial validates and extends the results to include women with scores up to 25.

Clinical outcomes in ER+ HER2 -node-positive breast cancer patients who were treated according to the Recurrence Score results: evidence from a large prospectively designed registry

The Recurrence Score® is increasingly used in node-positive ER+ HER2-negative breast cancer. This retrospective analysis of a prospectively designed registry evaluated treatments/outcomes in node-positive breast cancer patients who were Recurrence Score-tested through Clalit Health Services from 1/2006 through 12/2011 (N = 709). Medical records were reviewed to verify treatments/recurrences/survival. Median follow-up, 5.9 years; median age, 62 years; 53.9% grade 2; 69.8% tumors ≤ 2 cm; 84.5% invasive ductal carcinoma; 42.0% N1mi, and 37.2%/15.5%/5.2% with 1/2/3 positive nodes; 53.4% Recurrence Score < 18, 36.4% Recurrence Score 18–30, and 10.2% Recurrence Score ≥ 31. Overall, 26.9% received adjuvant chemotherapy: 7.1%, 39.5%, and 86.1% in the Recurrence Score < 18, 18–30, and ≥ 31 group, respectively. The 5-year Kaplan–Meier estimates for distant recurrence were 3.2%, 6.3%, and 16.9% for these respective groups and the corresponding 5-year breast cancer death estimates were 0.5%, 3.4%, and 5.7%. In Recurrence Score < 18 patients, 5-year distant-recurrence rates for N1mi/1 positive node/2–3 positive nodes were 1.2%/4.4%/5.4%. As patients were not randomized to treatment and treatment decision is heavily influenced by Recurrence Score, analysis of 5-year distant recurrence by chemotherapy use was exploratory and should be interpreted cautiously: In Recurrence Score < 18, recurrence rate was 7.7% in chemotherapy-treated (n = 27) and 2.9% in chemotherapy-untreated patients (n = 352); P = 0.245. In Recurrence Score 18–30, recurrence rate in chemotherapy-treated patients (n = 102) was significantly lower than in untreated patients (n = 156) (1.0% vs. 9.7% P = 0.019); in Recurrence Score ≤ 25 (the RxPONDER study cutoff), recurrence rate was 2.3% in chemotherapy-treated (n = 89) and 4.4% in chemotherapy-untreated patients (n = 488); P = 0.521. In conclusion, our findings support using endocrine therapy alone in ER+ HER2-negative breast cancer patients with micrometastases/1–3 positive nodes and Recurrence Score < 18.Genetic testing: Gene panel guides treatment for node-positive patientsWomen with breast cancer that has spread to the lymph nodes do well on anti-hormone treatment alone if they score under 18 on OncotypeDX. Salomon Stemmer from Rabin Medical Center in Petah Tikvah, Israel, and colleagues conducted the first analysis of a large prospectively designed registry in which patients with breast cancer cells in the underarm lymph nodes have taken the 21-gene expression analysis known as OncotypeDX to guide their treatment. Among the 709 women with node-positive, ER-positive, HER-negative disease, patients with test scores under 18 did just as well if they received chemotherapy or not in addition to anti-hormone treatment, whereas those with scores of 18 to 30 had significantly lower recurrence rates if they received both therapies. The findings suggest that only women with OncotypeDX scores under 18 can safely forgo chemotherapy.

Impact of the 12-Gene Colon Cancer Assay on Clinical Decision Making for Adjuvant Therapy in Stage II Colon Cancer Patients

OBJECTIVES To evaluate the impact of the 12-gene Colon Cancer Recurrence Score Assay-a clinically validated prognosticator in stage II colon cancer after surgical resection-on adjuvant treatment decisions in T3 mismatch repair proficient (MMR-P) stage II colon cancer in clinical practice. METHODS This retrospective analysis included all patients with T3 MMR-P stage II colon cancer (Clalit Health Services members) with Recurrence Score results (time frame January 2011 to May 2012). Treatment recommendations pretesting were compared with the treatments received. Changes were categorized as decreased (to observation alone/removing oxaliplatin from the therapy) or increased (from observation alone/adding oxaliplatin to the therapy) intensity. RESULTS The analysis included 269 patients; 58%, 32%, and 10% of the values were in the low (<30), intermediate (30-40), and high (≥41) score groups, respectively. In 102 patients (38%), treatment changed post-testing (decreased/increased intensity 76/26 patients). The overall impact was decreased chemotherapy use (45.0% to 27.9%; P < 0.001). Treatment changes occurred in all score groups, but more frequently in the high (change rate 63.0%; 95% confidence interval [CI] 42.3%-80.6%) than in the intermediate (30.6%; 95% CI 21.0%-41.5%) and low (37.6%; 95% CI 30.0%-45.7%) score groups. The direction of the change was consistent with the assay result, with increased intensity more common in higher score values and decreased intensity more common in lower score values. CONCLUSIONS Testing significantly affected adjuvant treatment in T3 MMR-P stage II colon cancer in clinical practice. The study is limited by its design, which compared treatment recommendations pretesting to actual treatments received post-testing, lack of a control group, and nonassessment of confounding factors that may have affected treatment decisions.