The methodology provided is sufficiently detailed to offer a uniformly applied, pragmatic starting point and improve consistency and reproducibility in the measurement of TILs for future studies.

Importance Tumor-infiltrating lymphocytes at diagnosis are reported to be prognostic in triple-negative breast cancer. Objective Here we evaluate the association of stromal tumor infiltrating lymphocytes (STILs) with recurrence-free survival (RFS) in N9831 HER2-positive patients treated with chemotherapy or chemotherapy plus trastuzumab. Design H&E tumor slides from patients on N9831 Arm A (standard AC→T chemotherapy) and Arm C (concurrent chemotherapy with trastuzumab) were assessed for STILs. STILs were quantitated in deciles and ≥60% STILs was used for the pre-specified categorical cutoff. The association between STILs and recurrence-free survival (RFS) was evaluated with Cox models. Setting Academic medical center Participants Tumor specimens from patients with early stage HER2+ breast cancer. Intervention(s) for clinical trials or exposure(s) for observational studies None. Main outcome measures Stromal tumor infiltrating lymphocytes (STILs) and their association with relapse-free survival. Results 489 pts from Arm A and 456 pts from Arm C were assessed with a median follow-up of 4.4 years. The 10 year Kaplan-Meier estimates for RFS in Arm A were 90.9% and 64.5% for patients with high STILs and low STILs, respectively (HR 0.23; 95%CI: 0.073 to 0.73; p=0.013). The 10 year estimates for RFS in Arm C were 80.0% and 80.1% for patients with high STILs and low STILs, respectively (HR 1.26; 95%CI: 0.5 to 3.2; p=0.63). The test for interaction between trastuzumab treatment and STILS status was statistically significant (p=0.026). In a multivariable analysis, STILs status remained significantly associated with RFS in Arm A and not significantly associated in Arm C (interaction p=0.042). Conclusions and relevance The analysis of N9831 patients found that STILs were prognostically associated with RFS in patients treated with chemotherapy alone, but not prognostically associated with RFS in patients treated with chemotherapy plus trastuzumab. High STILS were predictive of lack of trastuzumab benefit in contrast to a previously reported association between increased STILs and increased trastuzumab benefit in HER2 positive patients. Trial Registration Trial registration information: Clinicaltrials.gov, NCT00005970, https://clinicaltrials.gov/show/NCT00005970

To our knowledge, this study provides the first validation of the 12-gene Recurrence Score assay in stage III colon cancer without chemotherapy and showed the heterogeneity of recurrence risks in stage III as well as in stage II colon cancer.

Purpose The Recurrence Score test is validated to predict benefit of adjuvant chemotherapy. TransNEOS, a translational study of New Primary Endocrine-therapy Origination Study (NEOS), evaluated whether Recurrence Score results can predict clinical response to neoadjuvant letrozole. Methods NEOS is a phase 3 clinical trial of hormonal therapy ± adjuvant chemotherapy for postmenopausal patients with ER+, HER2-negative, clinically node-negative breast cancer, after six months of neoadjuvant letrozole and breast surgery. TransNEOS patients had tumors ≥ 2 cm and archived core-biopsy samples taken before neoadjuvant letrozole and subsequently sent for Recurrence Score testing. The primary endpoint was to evaluate clinical (complete or partial) response to neoadjuvant letrozole for RS < 18 versus RS ≥ 31. Secondary endpoints included evaluation of clinical response and rate of breast-conserving surgery (BCS) by continuous Recurrence Score result, ESR1 and PGR single-gene scores, and ER gene-group score. Results Of 295 TransNEOS patients (median age 63 years; median tumor size 25 mm; 66% grade 1), 53.2% had RS < 18, 28.5% had RS18–30, and 18.3% had RS ≥ 31. Clinical response rates were 54% (RS < 18), 42% (RS18–30), and 22% (RS ≥ 31). A higher proportion of patients with RS < 18 had clinical responses ( p < 0.001 vs. RS ≥ 31). In multivariable analyses, continuous Recurrence Score result ( p < 0.001), ESR1 score ( p = 0.049), PGR score ( p < 0.001), and ER gene-group score ( p < 0.001) were associated with clinical response. Recurrence Score group was significantly associated with rate of BCS after neoadjuvant treatment (RS < 18 vs. RS ≥ 31, p = 0.010). Conclusion The Recurrence Score test is validated to predict clinical response to neoadjuvant letrozole in postmenopausal patients with ER+, HER2-negative, clinically node-negative breast cancer. Electronic supplementary material The online version of this article (10.1007/s10549-018-4964-y) contains supplementary material, which is available to authorized users.

Context.—Nodal metastasis is one of the most important prognostic factors in colorectal carcinoma. The number of lymph nodes recovered and examined in resection specimens has been recently shown to be critical for proper staging and is associated with survival. Objective.—To assess the clinicopathologic factors that may be associated with the number of lymph nodes harvested from surgical resections. Design.—Clinicopathologic factors of 434 consecutive cases of colorectal cancers treated by surgical resection from a single tertiary medical center were retrospectively reviewed and correlated with number of lymph nodes recovered. Results.—Our data show that patient age, tumor location, and length of resected bowel segment were associated with number of lymph nodes harvested in surgical resections of colorectal cancer. The average number of lymph nodes was 18.2 and 17.8 for patients younger than 50 years and aged 50 through 60 years, respectively, whereas it was 14.4, 15.1, and 14.9 for patients aged 61 through 70 years, 71 through 80 years, and 80 years and older, respectively. More lymph nodes were present in resection specimens of cecum/ascending colon and descending colon cancers than in those of transverse colon, sigmoid colon, and rectal cancers. There was a linear increase in number of lymph nodes examined with increasing length of bowel resection specimens. In multivariate regression analysis, the factors that remained independent predictors of removal of 12 or more lymph nodes from resection specimens were tumor location and length of resected bowel segment. Conclusions.—The number of lymph nodes obtained in resection specimens for colorectal cancer was significantly associated with the length of resected segments of bowel, patient age, and location of the tumor.