Recently, phase I studies with novel antibody drug conjugates targeting HER2 suggested benefit in HER2-low patients -defined as immunohistochemistry(IHC) +1 or +2 FISH/ISH non-amplified, with advanced breast cancer(BC). Data on the prognostic value of HER2-low in early stage disease is scarce. The purpose of this study was to evaluate the impact of HER2-low status on response to neoadjuvant chemotherapy(NACT) and survival outcomes in early stage HER2negative BC. MethodsRecords from all BC patients treated with NACT from January 2007 to December 2018 in a single cancer center were retrospectively reviewed. Primary objective was to compare differences between pathologic complete response(pCR) and relapse free survival(RFS) in luminal HER2-low/HER2-0 and triple negative(TNBC) HER2-low/HER2-0. Results855 non-HER2-positive patients were identified. Median follow-up was 59 months. 542 had luminal BC (63.4%) and 313 TNBC (36.6%). 285 (33.3%) were HER2-low. Among luminal tumors, 145 had HER2 IHC+1 (26.8%) and 91 IHC+2/ISH non-amplified (16.8%). In TNBC, only 36 had HER2 IHC+1 (11.5%) and 13 IHC+2/ISH non-amplified (4.2%). Among luminal/HER2-low and luminal/HER2-0 population, there was a high proportion of clinical T3/4 (61.5% vs 69.2%, p=0.053), node positive (74.2% vs 66.3%, p=0.27) and stage III tumors (63.1% vs 65%, p=0.51). The same was true TNBC/HER-low as compared to TNBC/HER2-0, despite a non-statistically significant higher cT4 among TNBC/HER-low (32.7% vs. 19.3%, p=0.17). pCR was 13% in luminal/HER2-low versus 9.5% in luminal/HER2-0 (p=0.27), and 51% in TNBC/HER2-low versus 47% in TNBC/HER2-0 (p=0.64). 5y RFS was 72.1% in luminal/HER2-low and 71.7% in luminal/HER2-0 (p=0.47), and 75.6% in TNBC/HER2-low versus 70.8% in TNBC/HER2-0 (p=0.23). HER2-low status was not associated with RFS in multivariate analysis (HR 0.83, 95%CI 0.6-1.11, p=0.21). ConclusionOur data does not support HER2-low as a biologically distinct BC subtype, with no predictive effect on pCR after NACT nor prognostic value on survival outcomes.

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We aimed to use DECAS to estimate the long-term effectiveness of colonoscopy screening and perform a between-model comparison.Methods: We used DECAS to simulate a cohort of averaged-risk individuals from age of 20 to 90 for three scenarios: (1) no screening; (2) one colonoscopy screening at age of 55; (3) two colonoscopies at age of 55 and 65. We assumed the adenoma pathway accounted for 85% of the CRC development and the serrated pathway the other 15%, as well as 100% uptake of screening and surveillance colonoscopy for positive precancerous findings. Outcomes were reductions in CRC cumulative incidence and mortality in the two screening scenarios compared to no screening. We compared the results with incidence reductions estimated from another German CRC Markov model by Brenner et al.

We aimed to use DECAS to estimate the long-term effectiveness of colonoscopy screening and perform a between-model comparison.Methods: We used DECAS to simulate a cohort of averaged-risk individuals from age of 20 to 90 for three scenarios: (1) no screening; (2) one colonoscopy screening at age of 55; (3) two colonoscopies at age of 55 and 65. We assumed the adenoma pathway accounted for 85% of the CRC development and the serrated pathway the other 15%, as well as 100% uptake of screening and surveillance colonoscopy for positive precancerous findings. Outcomes were reductions in CRC cumulative incidence and mortality in the two screening scenarios compared to no screening. We compared the results with incidence reductions estimated from another German CRC Markov model by Brenner et al.

presented an event of interest for DDFS analyses. Five-year DDFS was 91,6%. Predictors for DDFS in univariate analysis were cT stage (c2¼45.408, p<0.001), AJCC Anatomic Stage Groups (c2¼ 110,784, p<0.001), and AJCC Clinical Prognostic Stage Groups (c2¼ 22,868, p¼0.001). In the multivariate analyse only AJCC anatomic stage groups retained significative results for DDFS (p<0,001).Conclusions: In our study, after pCR in breast cancer patients treated with NACT, only AJCC anatomic stage groups was significant for DDFS in the multivariate analyse. In this special population, these results emphasize the importance of meticulous staging at diagnosis and suggest the possibility of personalised follow-up and modulated adjuvant treatment after surgery based on AJCC anatomic stage groups.Legal entity responsible for the study: The authors.