Fibroblast growth factor receptor signaling in estrogen receptor-positive breast cancer: mechanisms and role in endocrine resistance.

Fibroblast Growth Factor Receptors (FGFRs) play a significant role in Estrogen Receptor-positive (ER+) breast cancer by contributing to tumorigenesis and endocrine resistance. This review explores the structure, signaling pathways, and implications of FGFRs, particularly FGFR1, FGFR2, FGFR3, and FGFR4, in ER+ breast cancer. FGFR1 is frequently amplified, especially in aggressive Luminal B-like tumors, and its amplification is associated with poor prognosis and treatment resistance. The co-amplification of FGFR1 with oncogenes like EIF4EBP1 and NSD3 complicates its role as a standalone oncogenic driver. FGFR2 amplification, though less common, is critical in hormone receptor regulation, driving proliferation and treatment resistance. FGFR3 and FGFR4 also contribute to endocrine resistance through various mechanisms, including the activation of alternate signaling pathways like PI3K/AKT/mTOR and RAS/RAF/MEK/ERK. Endocrine resistance remains a major clinical challenge, with around 70% of breast cancers initially hormone receptor positive. Despite the success of CDK 4/6 inhibitors in combination with endocrine therapy (ET), resistance often develops, necessitating new treatment strategies. FGFR inhibitors have shown potential in preclinical studies, but clinical trials have yielded limited success due to off-target toxicities and lack of predictive biomarkers. Current clinical trials, including those evaluating FGFR inhibitors like erdafitinib, lucitanib, and dovitinib, have demonstrated mixed outcomes, underscoring the complexity of FGFR signaling in breast cancer. The interplay between FGFR and other signaling pathways highlights the need for comprehensive molecular profiling and personalized treatment approaches. Future research should focus on identifying robust biomarkers and developing combination therapies to enhance the efficacy of FGFR-targeted treatments. In conclusion, targeting FGFR signaling in ER+ breast cancer presents both challenges and opportunities. A deeper understanding of the molecular mechanisms and resistance pathways is crucial for the successful integration of FGFR inhibitors into clinical practice, aiming to improve outcomes for patients with endocrine-resistant breast cancer.

Hormone receptor-positive early breast cancer in young women: A comprehensive review.

The incidence of breast cancer in ≤ 40 yr-old women (YWBC) has been steadily increasing in recent decades. Although this group of patients represents less than 10 % of all newly diagnosed BC cases it encompasses a significant burden of disease. Usually underrepresented in clinical trials, YWBCs are also characterized by late diagnoses and poorly differentiated, aggressive-subtype disease, partly explaining its poor prognosis along with a high recurrence risk, and high mortality rates. On the other hand, YWBC treatment poses unique challenges such as preservation of fertility, and long-term toxicity and adverse events. Herein, we summarize the current evidence in hormone receptor-positive YWBC including specific risk factors, clinicopathologic and genomic features, and available evidence on response to chemotherapy and endocrine therapy. Overall, we advocate for a more comprehensive multidisciplinary healthcare model to improve the outcomes and the quality of life of this subset of younger patients.

High linoleic acid levels in red blood cells predict a poor response to neoadjuvant chemotherapy in human epidermal growth factor receptor type 2-positive breast cancer patients.

OBJECTIVE: Polyunsaturated fatty acids are categorized as ω-3 or ⍵-6. Previous studies demonstrate that breast cancers display a high expression of fatty acid synthase and high fatty acid levels. Our study sought to determine if changes in plasma or red blood cell membrane fatty acid levels were associated with the response to preoperative (neoadjuvant) chemotherapy in non-metastatic breast cancer patients. METHODS: Our prospective study assessed fatty acid levels in plasma and red blood cell membrane. Response to neoadjuvant chemotherapy was evaluated by the presence or absence of pathologic complete response and/or residual cancer burden. RESULTS: A total of 28 patients were included. First, patients who achieved pathologic complete response had significantly higher neutrophil-to-lymphocyte ratio versus no pathologic complete response (P = 0.003). Second, total red blood cell membrane polyunsaturated fatty acids were higher in the absence of pathologic complete response (P = 0.0028). Third, total red blood cell membrane ⍵-6 polyunsaturated fatty acids were also higher in no pathologic complete response (P < 0.01). Among ⍵-6 polyunsaturated fatty acids, red blood cell membrane linoleic acid was higher in the absence of pathologic complete response (P < 0.01). Notably, plasma polyunsaturated fatty acid, ⍵-6, and linoleic acid levels did not have significant differences. A multivariate analysis confirmed red blood cell membrane linoleic acid was associated with no pathologic complete response; this was further confirmed by receiver operating characteristic analysis (specificity = 92.3%, sensitivity = 76.9%, and area under the curve = 0.855). CONCLUSIONS: Pending further validation, red blood cell membrane linoleic acid might serve as a predictor biomarker of poorer response to neoadjuvant chemotherapy in non-metastatic human epidermal growth factor receptor type 2-positive breast cancer. Measuring fatty acids in red blood cell membrane could offer a convenient, minimally invasive strategy to identifying patients more likely to respond or those with chemoresistance.

Calorie Restriction and Time-Restricted Feeding: Effective Interventions in Overweight or Obese Patients Undergoing Radiotherapy Treatment with Curative Intent for Cancer.

This study assesses the feasibility of calorie restriction (CR) and time-restricted feeding (TRF) in overweight and obese cancer patients who realized little to no physical activity undergoing curative radiotherapy, structured as a prospective, interventional, non-randomized open-label clinical trial. Of the 27 participants initially enrolled, 21 patients with breast cancer were selected for analysis. The participants self-selected into two dietary interventions: TRF, comprising a sugar and saturated fat-free diet calibrated to individual energy needs consumed within an 8 h eating window followed by a 16 h fast, or CR, involving a 25% reduction in total caloric intake from energy expenditure distributed across 4 meals and 1 snack with 55% carbohydrates, 15% protein, and 30% fats, excluding sugars and saturated fats. The primary goal was to evaluate the feasibility of these diets in the specific patient group. The results indicate that both interventions are effective and statistically significant for weight loss and reducing one's waist circumference, with TRF showing a potentially stronger impact and better adherence. Changes in the LDL, HDL, total cholesterol, triglycerides, glucose and insulin were not statistically significant.

Suboptimal use of ovarian function suppression in very young women with early breast cancer: a real-world data study.

PURPOSE: The incidence of breast cancer in young women (BCYW) has increased in recent decades. Malignant disease in this subset is characterized by its aggressiveness and poor prognosis. Ovarian function suppression (OFS) in these patients improves survival especially in hormone receptor-positive (HR +) cases. The Regan Composite Risk (RCR) is a prognostic tool to identify high-risk HR + BC candidates for OFS. Our study sought to characterize a Chilean cohort of early HR + BCYW assessing the use of OFS and its related prognosis and the utility of RCR in our patients. METHODS: This was a retrospective population cohort study that included ≤ 35-year-old early HR + /human epidermal growth factor receptor 2 -negative (HER2-) BC patients treated between 2001 and 2021. Analysis included clinical-pathological characteristics, treatment strategies, and survival. Also, we evaluated the association between RCR and survival. RESULTS: A total of 143 patients were included into our study, representing 2.9% of all early BC cases in our registry. Median age was 31 years old (range: 19-35). Most patients (93%) received endocrine therapy (ET). Of these, 18% received OFS. No survival differences were observed among treatment strategies. Median RCR score for patients treated with CT plus ET was significantly higher vs. ET alone (2.95 vs. 1.91; p = 0.0001). Conversely, patients treated with tamoxifen alone had significantly lower RCR scores vs. OFS (2.72 vs. 3.14; p = 0.04). Higher RCR scores were associated with poorer overall survival. CONCLUSION: Less than 20% of very young women with early HR + /HER2-BC in our cohort received OFS, in most cases, this involved surgical oophorectomy. RCR score was higher in patients that underwent CT and OFS and was associated with survival, regardless of treatment. We confirm the RCR score as a valuable prognostic tool to identify high-risk BC patients who could benefit from OFS.

Upper-Limb Disability and the Severity of Lymphedema Reduce the Quality of Life of Patients with Breast Cancer-Related Lymphedema.

Breast cancer-related lymphedema (BCRL) is characterized by arm swelling, pain, and discomfort, reducing the quality of life (QoL) of affected individuals. BRCL is caused via the blockage or disruption of the lymphatic vessels following cancer treatments, leading to an accumulation of fluid in the affected arm. While current BCRL rehabilitation treatments seek to reduce arm swelling, our study aimed to examine the impact of both the magnitude of lymphedema (ΔVolume) and arm disability on three dimensions of QoL: social, physical, and psychological. Using the Disabilities of the Arm, Shoulder, and Hand questionnaire (DASH) and the Upper Limb Lymphedema 27 questionnaire (ULL) in a group of 30 patients, we found that the magnitude of lymphedema (ΔVolume) was associated with the social dimension of QoL (r = 0.37, p = 0.041), but not with other dimensions. On the other hand, arm disability was associated with all evaluated dimensions of QoL (social, physical, and psychological: p < 0.001, p = 0.019, and p = 0.050 (borderline), respectively). These findings suggest that BCRL rehabilitation strategies should not only aim to reduce the magnitude of lymphedema but should also seek to improve or preserve arm functionality to enhance the QoL of BCRL patients.

Influence of SARS-CoV-2 mRNA Vaccine Booster among Cancer Patients on Active Treatment Previously Immunized with Inactivated versus mRNA Vaccines: A Prospective Cohort Study.

Cancer patients on chemotherapy have a lower immune response to SARS-CoV-2 vaccines. Therefore, through a prospective cohort study of patients with solid tumors receiving chemotherapy, we aimed to determine the immunogenicity of an mRNA vaccine booster (BNT162b2) among patients previously immunized with an inactivated (CoronaVac) or homologous (BNT162b2) SARS-CoV-2 vaccine. The primary outcome was the proportion of patients with anti-SARS-CoV-2 neutralizing antibody (NAb) seropositivity at 8-12 weeks post-booster. The secondary end points included IgG antibody (TAb) seropositivity and specific T-cell responses. A total of 109 patients were included. Eighty-four (77%) had heterologous vaccine schedules (two doses of CoronaVac followed by the BNT162b2 booster) and twenty-five had (23%) homologous vaccine schedules (three doses of BNT162b2). IgG antibody positivity for the homologous and heterologous regimen were 100% and 96% (p = 0.338), whereas NAb positivity reached 100% and 92% (p = 0.13), respectively. Absolute NAb positivity and Tab levels were associated with the homologous schedule (with a beta coefficient of 0.26 with p = 0.027 and a geometric mean ratio 1.41 with p = 0.044, respectively). Both the homologous and heterologous vaccine regimens elicited a strong humoral and cellular response after the BNT162b2 booster. The homologous regimen was associated with higher NAb positivity and Tab levels after adjusting for relevant covariates.

Access disparities and underutilization of germline genetic testing in Chilean breast cancer patients.

PURPOSE: Latin American reports on genetic cancer risk assessments are scarce. In Chile, current breast cancer (BC) guidelines do not define strategies for germline genetic testing. Our study sought to quantify the disparities in access to genetic testing in Chilean BC patients, according to international standards and their clinical characteristics to explore improvement strategies. METHODS: Retrospective analysis of invasive BC databases including patients treated in a Public Hospital (PH) and in an Academic Private Center (AC) in Santiago, Chile between 2012 and 2021. RESULTS: Of 5438 BC patients, 3955 had enough data for National Comprehensive Cancer Network (NCCN) categorization. From these, 1911 (48.3%) fulfilled NCCN criteria for germline testing, of whom, 300 were tested for germline mutations and 268 with multigene panels. A total of 65 pathogenic variants were found in this subset. As expected, BRCA1/2 mutations were the most frequent (17.7%). Access to genetic testing was higher in AC versus PH (19.6% vs. 10.3%, p = 0.0001). Other variables associated with germline genetic testing were BC diagnosis after 2018, being 45 years old or younger at diagnosis, BC family history (FH), FH of ovarian cancer, non-metastatic disease, and triple-negative subtype. CONCLUSION: In our cohort, 15% of BC patients who met NCCN criteria for germline testing were effectively tested. This percentage was even lower at the PH. Current recommendations encourage universal genetic testing for BC patients; however, our findings suggest that Chile is far from reaching such a goal and national guidelines in this regard are urgently needed. To our knowledge, this is the first study of its kind in Chile and Latin America.

Clinical characteristics, risk factors, and outcomes in Chilean triple negative breast cancer patients: a real-world study.

BACKGROUND: Latin American (LA) studies on triple-negative breast cancer (TNBC) and their characteristics are scarce. This forces physicians to make clinical decisions based on data obtained from studies that include non-Hispanic patients. Our study sought to obtain local epidemiological data, including risk factors and clinical outcomes from a Chilean BC registry. METHODS: This was a retrospective population-cohort study that included patients treated at a community hospital (mid-low income) or an academic private center (high income), in the 2010-2021 period. Univariate and multivariate analyses were performed to identify prognostic factors associated with survival. RESULTS: 647 out of 5,806 BC patients (11.1%) were TNBC. These patients were younger (p = 0.0001) and displayed lower rates of screening-detected cases (p = 0.0001) compared to non-TNBC counterparts. Among TNBC patients, lower income (i. e., receiving treatment at a community hospital) was associated with poorer overall survival (HR: 1.53; p = 0.0001) and poorer BC specific survival (HR: 1.29; p = 0.004). Other risk factors showed no significant differences between TNBC and non-TNBC. As expected, 5-year OS was significantly shorter on TNBC versus non-TNBC patients (p = 0.00001). In our multivariate analyses TNBC subtype (HR: 2.30), locally advanced stage (HR: 7.04 for stage III), lower income (HR: 1.64), or non-screening detected BC (HR: 1.32) were associated with poorer OS. CONCLUSION: To the best of our knowledge, this is the largest LA cohort of TNBC patients. Interestingly, the proportion of TNBC among Chileans was smaller compared to similar studies within LA. As expected, TNBC patients had poorer survival and higher risk for early recurrence versus non-TNBC. Other relevant findings include a higher proportion of premenopausal patients among TNBC. Also, mid/low-income patients that received medical attention at a community hospital displayed lower survival versus private health center counterparts.

Palbociclib in advanced stage hormone receptor-positive breast cancer: real-world data from a Chilean multicentre registry.

Background: The addition of cyclin-dependent kinases inhibitors (CDKi) to endocrine therapy (ET) as the first- or second line treatment improves progression-free and overall survival (OS) in hormone receptor-positive, HER2 negative (HR+/HER2-) advanced stage breast cancer (ABC). Our study compared survival rates and prognostic factors in Chilean patients that used palbociclib as first or subsequent (≥second) lines of treatment in a real-world setting. Methods: Our retrospective population-cohort study included HR+/HER2- ABC patients. We calculated 5-year OS and performed a multivariate analysis to determine prognostic factors. Results: A total of 106 patients were included. Median age was 49 years (19-86), 28.3% (30) had de novo stage IV disease; 63% received palbociclib with ET as first line, 54% of them with aromatase inhibitor over fulvestrant. Median OS for the entire cohort was 99 months and 5-year OS was 69%. Patients that received first line palbociclib had a 5-year OS of 89% versus 43% for ET monotherapy or ≥second line palbociclib (p = 0.0062). Multivariate analysis showed that the year at diagnosis and CDKi timing (first line versus ≥second line) were significantly associated with OS. Conclusion: Our real-world data show that first-line CDKi + ET provides a statistically significant benefit in OS versus ≥second line in HR+/HER2- ABC patients.

Obesity is associated with early recurrence on breast cancer patients that achieved pathological complete response to neoadjuvant chemotherapy.

Pathological complete response (pCR) after neoadjuvant chemotherapy (NCT) is associated with good long-term prognosis in breast cancer (BC) patients. However, some patients still recur and eventually die from this disease. For years, clinical stage at diagnosis has been consistently linked to recurrence and survival in the pCR setting. Herein, we aimed to identify other potential predictors of recurrence and survival in patients that achieved pCR. We performed a retrospective analysis of patients diagnosed between 2011 and 2020 in our center. We calculated overall survival (OS), invasive disease-free survival (IDFS), distant disease-free survival (DDFS), and BC-specific survival (BCSS). Among the 241 patients included into our study 36% were obese (Body Mass Index (BMI) > 29.9 kg/m2) and 47% were stage III. Multivariate analysis confirmed that obesity was a significant risk factor associated with early recurrence and poorer survival in these patients. In summary, obesity and clinical stage predict early recurrence and poorer survival in patients that achieved pCR after NCT. Pending further investigation and based on our findings we speculate that weight management could be beneficial for this subset of patients. To our knowledge, this is the first Latin American report linking obesity and recurrence within this setting.

Contrast-enhanced mammography predicts pathological response after neoadjuvant chemotherapy in locally advanced breast cancer.

Introduction: Recently, contrast-enhanced mammography (CEM) has emerged as a reliable alternative to breast magnetic resonance imaging (MRI) for the assessment of pathological response in breast cancer patients. Our study sought to determine the diagnostic accuracy of CEM to predict pathological complete response (pCR) in patients who received neoadjuvant chemotherapy (NACT). Methods: We retrieved the medical records of patients who underwent NACT at our institution. Using post-surgery pCR, morphological evidence and CEM enhancement tumours were classified as follows: 1) radiologic complete response (rCR); 2) functional radiological complete response (frCR); and 3) non-complete response. Initially, we used multivariate analyses adjusted by clinical variables and frCR or rCR to determine which variables affected pathological response. Then, CEM diagnostic accuracy to discriminate pCR was assessed using receiver operating characteristic curves in univariate and multivariate models including either frCR or rCR. Results: A total of 48 patients were included in our study. Most patients (68.7%) were hormone receptor (HR)+ and 41.6% (20) of the patients achieved pCR. Using univariate logistic regression analyses we found that HR status, HER2 status, rCR and frCR had a significant impact on CEM diagnostic accuracy. Exploratory analyses found that CEM sensitivity was higher for HR- tumours. Multivariate logistic regression analyses found 60% sensitivity, 92.9% specificity and 79.2% accuracy in a model that included clinical variables and rCR. Conclusion: CEM is a reliable alternative to high-cost, time-consuming breast MRI that predicts pCR in patients undergoing NACT; CEM diagnostic accuracy was higher among patients who harboured HR- tumours.

Estimating the impact of the COVID-19 pandemic on diagnosis and survival of five cancers in Chile from 2020 to 2030: a simulation-based analysis.

BACKGROUND: The COVID-19 pandemic has strained health system capacity worldwide due to a surge of hospital admissions, while mitigation measures have simultaneously reduced patients' access to health care, affecting the diagnosis and treatment of other diseases such as cancer. We estimated the impact of delayed diagnosis on cancer outcomes in Chile using a novel modelling approach to inform policies and planning to mitigate the forthcoming cancer-related health impacts of the pandemic in Chile. METHODS: We developed a microsimulation model of five cancers in Chile (breast, cervix, colorectal, prostate, and stomach) for which reliable data were available, which simulates cancer incidence and progression in a nationally representative virtual population, as well as stage-specific cancer detection and survival probabilities. We calibrated the model to empirical data on monthly detected cases, as well as stage at diagnosis and 5-year net survival. We accounted for the impact of COVID-19 on excess mortality and cancer detection by month during the pandemic, and projected diagnosed cancer cases and outcomes of stage at diagnosis and survival up to 2030. For comparison, we simulated a no COVID-19 scenario in which the impacts of COVID-19 on excess mortality and cancer detection were removed. FINDINGS: Our modelling showed a sharp decrease in the number of diagnosed cancer cases during the COVID-19 pandemic, with a large projected short-term increase in future diagnosed cases. Due to the projected backlog in diagnosis, we estimated that in 2021 there will be an extra 3198 cases (95% uncertainty interval [UI] 1356-5017) diagnosed among the five modelled cancers, an increase of nearly 14% compared with the no COVID-19 scenario, falling to a projected 10% increase in 2022 with 2674 extra cases (1318-4032) diagnosed. As a result of delayed diagnosis, we found a worse stage distribution for detected cancers in 2020-22, which is estimated to lead to 3542 excess cancer deaths (95% UI 2236-4816) in 2022-30, compared with the no COVID-19 scenario, among the five modelled cancers, most of which (3299 deaths, 2151-4431) are projected to occur before 2025. INTERPRETATION: In addition to a large projected surge in diagnosed cancer cases, we found that delays in diagnosis will result in worse cancer stage at presentation, leading to worse survival outcomes. These findings can help to inform surge capacity planning and highlight the importance of ensuring appropriate health system capacity levels to detect and care for the increased cancer cases in the coming years, while maintaining the timeliness and quality of cancer care. Potential delays in treatment and adverse impacts on quality of care, which were not considered in this model, are likely to contribute to even more excess deaths from cancer than projected. FUNDING: Harvard TH Chan School of Public Health. TRANSLATIONS: For the Spanish and Portuguese translations of the abstract see Supplementary Materials section.

Screen-detected breast cancer is associated with better prognosis and survival compared to self-detected/symptomatic cases in a Chilean cohort of female patients.

PURPOSE: The implementation of national breast cancer (BC) screening programs in Latin America has been rather inconsistent. Instead, most countries have opted for "opportunistic" mammogram screenings on the population at risk. Our study assessed and compared epidemiological, clinical factors, and survival rates associated with BC detected by screening (SDBC) or self-detected/symptomatic (non-SDBC) in Chilean female patients. METHODS: Registry-based cohort study that included non-metastatic BC (stage I/II/III) patients diagnosed between 1993 and 2020, from a public hospital (PH) and a private university cancer center (PC). Epidemiological and clinical data were obtained from medical records. RESULTS: A total of 4559 patients were included. Most patients (55%; n = 2507) came from PH and were diagnosed by signs/symptoms (non-SDBC; n = 3132, 68.6%); these patients displayed poorer overall (OS) and invasive disease-free survival (iDFS) compared to SDBC. Importantly, the proportion of stage I and "luminal" BC (HR + /HER2 -) were significantly higher in SDBC vs. non-SDBC. Finally, using a stage/subset-stratified age/insurance-adjusted model, we found that non-SDBC cases are at a higher risk of death (HR:1.75; p < 0.001). In contrast, patients with PC health insurance have a lower risk of death (HR: 0.60; p < 0.001). CONCLUSION: We confirm previous studies that report better prognosis/survival on SDBC patients. This is probably due to a higher proportion of stage I and luminal-A cases versus non-SDBC. In turn, the survival benefit observed in patients with PC health insurance might be attributed to a larger proportion of SDBC. Our data support the implementation of a systematic BC screening program in Chile to improve patient prognosis and survival rates.

Pathological complete response to neoadjuvant chemotherapy, but not the addition of carboplatin, is associated with improved survival in Chilean triple negative breast cancer patients: a report of real world data.

BACKGROUND: Breast cancer (BC) is the leading cause of cancer death for Chilean women. About 11% of cases are triple-negative (TN) BC. These are characterised by poor prognosis, higher risk of early recurrence and visceral dissemination versus other BC subtypes. Current standard treatment for early-stage non-metastatic TNBC patients consists of neoadjuvant chemotherapy (NACT) followed by surgery and radiotherapy. Pathological complete response (pCR) to NACT is associated with an increase in survival rates. In general, NACT and adjuvant regimens involve similar cytotoxic drugs. Recent studies have postulated that the use of platinum compounds in TNBC would increase response rates. However, their effects on patient survival remain uncertain. MATERIALS AND METHODS: We retrieved and analysed medical records from a total of 156 Chilean stage I-III TNBC female patients that received NACT and compared survival rates using carboplatin (Cb)-containing versus non-Cb-containing regimens at two health cancer centres. RESULTS: Median age was 51 years (range: 24-81); 13.5% (n = 21) received Cb-containing regimens, 80.1% (n = 125) received sequential anthracyclines plus taxanes; 29.5% (n = 46) of the total group achieved pCR, 28% for the standard treatment and 35% (n = 8) for the Cb-containing group (p = 0.59). We confirmed pCR was associated with prolonged overall survival, invasive and distant disease-free survival (Log-rank p = 0.0236). But the addition of Cb was not associated with differences in survival measures (Log-rank p = 0.5216). CONCLUSIONS: To the best of authors' knowledge, this is the first report on real-world data in the Chilean population assessing the effect of Cb-containing NACT in TNBC. The authors' results suggest no survival benefit by the addition of Cb to standard NACT. However, we confirm an increase in survival associated to pCR regardless of treatment.

Better overall survival in patients who achieve pathological complete response after neoadjuvant chemotherapy for breast cancer in a Chilean public hospital.

INTRODUCTION: There is extensive evidence associating the response to neoadjuvant chemotherapy (NeoCT) with breast cancer (BC) survival. However, to the author's knowledge, there is no published data in Chile. The objective of the study is to evaluate whether achieving pathological complete response (pCR) after NeoCT is associated with greater survival and lower risk of recurrence in a Chilean Public Health Service. METHODS: Retrospective analysis of a database. Patients with a diagnosis of Stages I-III BC who received NeoCT between 2009 and 2019 were included. Clinical and pathological information were extracted from the clinical records. BC subtypes were defined using hormone receptor (HR) information (HR: oestrogen and/or progesterone) and epidermal growth factor type 2 (HER2), being divided into four groups: HR+/HER2-, HR+/HER2+, HR-/HER2+, HR-/HER2-. pCR was defined as the absence of invasive cancer in the breast and axilla (ypT0/is N0) after NeoCT. RESULTS: Of 3,092 patients, 17.2% received NeoCT. Of these, 40.2% corresponded to HR+/HER2-, 20.9% HR+/HER2+, 18.2% HR-/HER2+ and 20.7% HR-/HER2-. Overall, 24.8% achieved pCR, being the lowest for HR+/HER2- (10.3%) and the highest for HR-/HER2+ (53.2%). In the multivariable analysis, family history, HER2+ and type of chemotherapy were associated with a greater probability of pCR. With a median follow-up of 40 months, the overall survival and metastasis-free survival (MFS) at 3 years were greater for the group with pCR compared to that which did not achieve it (90.5% versus 76.7%, p = 0.03 and 88.5% versus 71.4%, p = 0.003, respectively). The multivariable analysis confirmed this finding. Brain MFS was similar in both groups. CONCLUSION: NeoCT is associated with greater pCR in aggressive BC subtypes. In those, achieving pCR was associated with better survival in our study. To the author's knowledge, this is the first study which evaluates the relation between pCR and BC subtypes in a Chilean public hospital.

First-line endocrine therapy for advanced breast cancer. A real-world study at a Latin American university health institution.

Objective: Clinical guidelines recommend the use of endocrine therapy (ET) in advanced hormone receptor positive (HR+) human epidermal growth factor receptor type 2 negative (HER2-) breast cancer (BC) patients in the absence of visceral disease or ET resistance. Furthermore, studies indicate similar response and survival rates using ET or cytotoxic chemotherapy (CT).Methods: Herein, we assessed clinical characteristics, type of systemic therapy and survival rates of advanced HR + HER2-BC patients in our database.Results: A total of 172 advanced HR + HER2-BC patients were treated at our institution between 1997 and 2019. Sixty percent received first-line ET (4% received combined ET). Median age of this subset was 55 years (range: 30-86). Similarly, the median age of patients that received CT was 54 years (range: 21-83). Over time, 30% of patients received ET in the 2000-2005 period; this increased to 70% in the 2016-2019 period (p = .045). Overall survival (OS) was 97 months and 51 months for patients treated with ET or CT, respectively (p = .002).Conclusions: To the best of our knowledge this is the first study assessing the use of ET in Chilean advanced HR + HER2-BC patients. Several patients in our institution receive CT without indication. The increase in ET usage over time can be attributed to better and faster immunohistochemical detection methods for Estrogen Receptor (ER), changes in educational and government policies, and a wider variety of ET options. Finally, clinical trials have failed to demonstrate a substantial benefit of CT over ET in this setting.

[Atypical hemolytic uremic syndrome. Report of two cases treated with Eculizumab]. / Síndrome hemolítico urémico atípico en tratamiento con eculizumab. Casos clínicos.

Hemolytic uremic syndrome (HUS) is a type of thrombotic microangiopathy where organic damage predominates in the kidney. Atypical HUS (aHUS) is a rare disease that affects young adults and causes terminal chronic renal failure ending in dialysis, in most cases. It also recurs after kidney transplantation. aHUS is associated with genetic defects of the alternative complement pathway or its activation by other factors such as drugs, autoimmune diseases, infections, malignant hypertension and ischemia-reperfusion. We report two women aged 17 and 25 years old with catastrophic aHUS. In both cases, complement amplifying factors (drugs and infections) were added and acted on a genetic vulnerability to precipitate complement activation and produce aHUS. Both patients developed terminal renal failure and had to undergo hemodialysis. Fortunately, after a broad etiological study, it was possible to make the diagnosis of aHUS and start treatment with Eculizumab, a monoclonal antibody that changed the natural history of aHUS. It inhibits complement activity controlling microangiopathy and preventing the development of end-stage renal disease. It also improves the success rate in kidney transplantation. In the case of our patients, both discontinued dialysis after chronic treatment with Eculizumab.

Síndrome hemolítico urémico atípico en tratamiento con eculizumab: casos clínicos / Atypical hemolytic uremic syndrome: report of two cases treated with Eculizumab

Hemolytic uremic syndrome (HUS) is a type of thrombotic microangiopathy where organic damage predominates in the kidney. Atypical HUS (aHUS) is a rare disease that affects young adults and causes terminal chronic renal failure ending in dialysis, in most cases. It also recurs after kidney transplantation. aHUS is associated with genetic defects of the alternative complement pathway or its activation by other factors such as drugs, autoimmune diseases, infections, malignant hypertension and ischemia-reperfusion. We report two women aged 17 and 25 years old with catastrophic aHUS. In both cases, complement amplifying factors (drugs and infections) were added and acted on a genetic vulnerability to precipitate complement activation and produce aHUS. Both patients developed terminal renal failure and had to undergo hemodialysis. Fortunately, after a broad etiological study, it was possible to make the diagnosis of aHUS and start treatment with Eculizumab, a monoclonal antibody that changed the natural history of aHUS. It inhibits complement activity controlling microangiopathy and preventing the development of end-stage renal disease. It also improves the success rate in kidney transplantation. In the case of our patients, both discontinued dialysis after chronic treatment with Eculizumab.