Factores predictivos de respuesta patológica completa a tratamiento sistémico neoadyuvante en pacientes con cáncer invasor de mama Luminal B

Abstract

Introduction The identification of predictive factors of complete pathological response(pCR) to NAQT in luminal B breast cancer will allow us to select patients who can benefit from receiving neoadjuvant therapy and, therefore, look for alternatives therapeutics for potentially resistant patients. Objectives To determine predictive factors of pCR in patients with luminal B and luminal-HER-2 breast cancer after NAQT. To determine predictive factors of an axillary pathological complete response (ypN0) of node positive luminal B and luminal-HER-2 breast cancer to NAQT. For evaluating the predictive value of the pCR of different inflammatory index before and after NAQT. Development and validation of nomogram or score to predict pCR in patients with luminal B and luminal-HER-2 breast cancer after NAQT based on clinicopathological features. Material and Methods Observational, retrospective, single-centered, historical cohort study, based on the analysis of a database of 244 patients diagnosed with invasive breast carcinoma after neoadjuvant treatment between 2018-2023, that meet the inclusion and exclusion criteria. A descriptive study of the series was carried out; univariate and multivariate statistical analyses were used to examine the relationship between the complete pathological response with clinical-demographic, gynecological, anatomopathological, systemic treatment, surgical treatment and analytical variables). With the results, a predictive model was developed based on the proposed variables. Results After analyzing a total of 244 patients with luminal B breast cancer (HER-2 +/HER-2-), treated with neoadjuvant chemotherapy, a tumor pCR was obtained in 25.4% of the patients, with 11.3% of the pCR in HER-2 - patients and 45.1% in HER-2 +, a significant association was observed with age (p<0.043), hypertension (p<0.010), body mass index (p<0.007), BIRADs (p<0.004), cT (p<0.025), size prior to systemic therapy (p<0.012), tumor differentiation grade (p<0.036), ER 30%(p<0.002), 50% (p<0.0001), PR (p<0.033), HER-2(p<0.0001), mitotic index (p<0.019), radiological response criteria in the evaluation of systemic treatments (p<0.0001), size of lymph node metastasis (p<0.0001) y extracapsular extension (p<0.008). An axillary pCR was obtained in 30 cases (25.4%) in previously positive cN patients, which showed a statistically significant association with the expression of ER (p<0.0001), HER-2(p<0.0001), tumor size postneoadjuvant (p<0.021), radiological response criteria in the evaluation of systemic treatments (p<0.015), LVI (p<0.0001), PNI (p<0.034), tumoral size (p<0.0001) and % carcinoma in situ (p<0.0001), subsequently studied in a multivariate análisis. No statistical correlation was found. 24.6% of the patients (n=244) obtained tumor and axillary pCR, of which 10.6% had HER-2-negative luminal B tumor and 44.1% overexpressed HER-2. When evaluating the predictive value of the different inflammatory biomarkers, a significant association of SII before neoadjuvant therapy with tumor pCR (p<0.018) and total pCR (p<0.020) was observed, as well as, between PIV before to neoadjuvant treatment and total pCR (p<0.035) in patients with HER-2 overexpression. Furthermore, an association was found between PIV after neoadjuvant therapy and axillary pCR in HER-2 - (p<0.043). A predictive model was developed for tumor pCR (hypertension (p<0.024), BIRADs (p<0.017), PR (p<0.017), HER-2 (p<0.0001), ER 30 % (p<0.013), SII before neoadjuvant therapy (p<0.002)) and other predictive model for total pCR (hypertension (p<0.028), BIRADs (p<0.031), PR (p<0.036), HER-2 (p<0.0001), ER 30 % (p<0.041), SII before neoadjuvant therapy (p<0.002)). The AUC of the ROC curve in the tumor pCR-model is 0.821 with a p<0.0001 and that of the total pCR-model is 0.821 with a p<0.0001. Internal validation of the models was also carried out with Bootstrap techniques. Conclusions In luminal B invasive breast carcinoma, age, hypertension, body mass index, BIRADs, cT, size before to systemic therapy, tumor differentiation grade, ER 10%, 50%, PR, HER-2, mitotic index, radiological response criteria are found as predictor variables of tumor pCR after neoadjuvant treatment. In the case of axillary pCR, only ER 50%, HER-2, and response to neoadjuvant chemotherapy by imaging and postneoadjuvant size are observed as predictor variables. Total pCR is related to age, hypertension, body mass index, menopause, BIRADs, cT, size before to systemic therapy, tumor differentiation grade, ER 10%, 50%, PR, HER-2, mitotic index, radiological response criteria and postneoadjuvant size. An association was observed between preneoadjuvant SII and tumor and total pCR. PIV before neoadjuvant treatment was related to total pCR. After a multivariate study, it is possible to develop a predictive model for tumor pCR and total pCR based on the variables hypertension, BIRADs, PR, ER 30%, HER-2, and SII after neoadjuvant therapy.