Cervical Cancer (CC) is a significantly prevalent disease in developing countries. Currently, targeted therapies are not a primary standard of care in CC. This information could be crucial for developing directed therapies and patient screening for biomarkers that would allow personalised treatment of CC. This systematic review aimed to estimate the prevalence of potential therapeutic targets such as the epidermal growth factor receptor (EGFR) and the PI3K/Akt/mTOR and Ras/Raf/MAPK pathways in patients with CC, identified through genomic and non-genomic testing. Studies were identified through an ad-hoc search strategy from the available on MEDLINE (Ovid), CENTRAL, LILACS, SCOPUS, through the Clinical Trial registry on Clinicaltrials.gov, International Clinical Trials Registry Platform, RENIS (Argentine National Registry of Health Research) and grey literature sources. We included 74 studies which represented a total pool of 7,862 participants. Forty-five studies informed mutations of EGFR, with a combined positivity rate of 53% (95%CI: 45%-60%; I 2 = 95%). Twenty studies informed the presence of mutations in PIK3CA with a combined positivity rate of 30% (95%CI: 21%-39%; I 2 = 96%). Twentythree studies reported a mutation in Ras, with a combined positivity rate of 14% (95%CI: 8%-21%; I 2 = 95%). Raf mutations were informed in six studies. Six studies informed the presence of Akt mutations, two studies informed mTOR mutations and only one study reported mutations of MAPK. The most frequently described therapeutic targets were EGFR, and the PIK3CA and Ras pathways, though inconsistency in positivity rates was significant. Our study did not allow the identification of any specific clinical characteristics that might explain the observed heterogeneity. Despite the overall good quality of the included studies, the applicability of these results to patients' general population with CC is still unclear.
INTRODUCTION Axillary node metastasis is one of the most important prognostic factors to be considered in the treatment of Breast Cancer. Although the association between axillary metastasis and pathologic tumor size has been extensively studied, the correlation between the immunohistochemical (IHC) subtype and axillary compromise has not. The aim of this study was to evaluate the correlation between the immunohistochemical subtype of Breast Cancer (BC) and axillary extension. As secondary outcomes, we assessed disease-free (DFS) and overall survival (OS). MATRERIALS AND METHODS 1413 consecutive patients who underwent surgery for invasive primary breast cancer at the Hospital Italiano de Buenos Aires between the years of 2007 and 2012 were included. Patients presenting with stage IV disease were excluded. We analyzed the clinical and pathologic data of patients who were submitted to either sentinel node biopsy (SNB) or axillary lymph node dissection (ALND). Based on IHC, tumors were classified into four groups: Luminal A (RE+ RP+ HER2-, KI 67 <14%), Luminal B (RE+ RP+, HER+/ KI 67 >15%), HER 2 (RE- RP- HER+) and Triple Negative (TNBC) breast cancer (RE- RP- HER-). RESULTS We evaluated 1413 patients, among which 1248 patients were eligible for inclusion and analysis. In this population, 386 patients (31%) had axillary metastasis. By considering the Luminal A subtype population as our control group, we found that axillary metastasis was significantly increased in the Luminal B and HER2 positive subtypes (p<0.0001), but not in the TNBC subtype (p=0.4468). When adjusted by tumor size and IHC, in tumors smaller than 2 cm (pT1), the Luminal B and TN subtypes significantly increase the risk of node metastasis with an OR 2.73 (CI95% 1.73 - 4.31, P > 0.000), and OR 2.05 (CI95% 1.13 -3.70, P=0.017) respectively. In the case of HER2 positive tumors, the odds ratio for axillary extension was 6.62 (CI95% 3.02 - 14.50, P > 0.000). The median follow-up was 29 months (17- 44 months), and the overall survival estimated by Kaplan-Meier was 91% (CI95% 87-94), with a disease-free survival of 62% (CI95% 28-83). DISCUSSION In this cohort, immunohistochemical subtype was an important independent predictor of axillary metastasis. Tumors smaller than 2 cm, that overexpress HER2 in absence of estrogen and progesterone receptor, have up to six times greater incidence of axillary extension than those belonging to the Luminal A subtype. Luminal B and Triple Negative cancers on the other hand appear to present twice the risk when compared to the Luminal A subtype. Citation Format: Maria F Calvo, Carola Allemand, Francisco H Corrao, Roberto Orti, Liliana B Zamora, Maria C Riggi, Maria F Ilzarbe, Jorge Piccolini, Alejandra Wernicke, Sebastian Gogorza, Gustavo Izbizky, Claudio Lorusso. Impact of the immunohistochemical subtypes of breast cancer on prediction of axillary metastasis: Experience of one breast center in Argentina [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-08-44.
Introduction: At present, more than half of patients diagnosed with early-stage breast cancer (BC) and express hormonal receptors will receive some adjuvant chemotherapy scheme, but only a few of them would benefit in terms of survival. Genomic platforms allow a better understanding of the heterogeneity of different types of hormonal receptor-positive and HER2-negative BC. They have proven their validity as tools to identify those patients who will obtain a clear benefit with the indication of chemotherapy treatment. The aim of this study is to analyze the use of the genomic platform, namely, Oncotype Dx® and its impact on the indication of adjuvant treatment, evaluated mainly as the change in treatment indication. Methods: Multicenter observational cohort study was performed in different Mastology units in Argentina. Patients underwent the Oncotype Dx to clarify the adjuvant treatment. Treatment decisions were settled before and after performing Oncotype Dx. Results: From January 2013 to December 2018, 211 patients with luminal A or B and HER2-negative breast carcinomas, who underwent the Oncotype Dx, were included. Based on our records, 40% of the patients change the indication of adjuvant treatment after the performance of the Oncotype Dx. Of these, 24% of patients who underwent initial endocrine therapy only adjusted their treatment with the addition of chemotherapy. Among patients with an initial CTH recommendation, 49% were able to receive endocrine therapy only when, due to traditional prognostic factors, they would have received chemotherapy. Conclusions: In our population, the use of the Recurrence Score was clinically significant in relation to the change of the established treatments. Consequently, it is a very important tool and a decisive factor in the adjuvant indication in patients with positive hormonal receptors and HER2neu-negative early BC.
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