Browsing by Author "Gomez, HL"

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A biomarker study in Peruvian males with breast cancer
(Baishideng Publishing Group, 2021) Castaneda, Carlos; Castillo, Miluska; Bernabe, LA; Sanchez, J; Torres, E; Suarez, N; Tello, K; Fuentes, H; Dunstan, J; De La Cruz, M; Cotrina, JM; Abugattas, J; Guerra, H; Gomez, HL
AIM:To investigate clinicopathological features and biomarkers of BC tumors in males and their prognostic value in Peruvian population. METHODS: This study looked at a single-institution series of 54 Peruvian males with invasive BC who were diagnosed from Jan 2004 to June 2018. Standard pathological features, TIL levels, MMR proteins, AR immunohistochemistry staining, and PIK3CA gene mutations were prospectively evaluated in cases with available paraffin material. Percentage of AR and estrogen receptor (ER) positive cells was additionally calculated by software after slide scanning. Statistical analyses included association tests, intraclass correlation test and Kaplan Meier overall survival curves. RESULTS: The median age was 63 years and most cases were ER-positive (85.7%), HER2 negative (87.2%), Luminal-A phenotype (60%) and clinical stage II (41.5%) among our male breast tumors. Median TIL was 10% and higher levels tended to be associated with Luminal-B phenotype and higher grade. AR-positive was found in 85.3% and was correlated with ER (intraclass index of 0.835, P < 0.001). Loss of MMR proteins was found in 15.4% and PIK3CA mutation (H1047R) in 14.3% (belonged to the Luminal-A phenotype). Loss of MMR proteins was associated with AR-negative (P = 0.018) but not with ER (P = 0.43) or TIL (P = 0.84). Early stages (P < 0.001) and lower grade (P = 0.006) were associated with longer overall survival. ER status, phenotype, AR status, TIL level, MMR protein loss nor PIK3CA mutation was not associated with survival (P > 0.05). CONCLUSION: Male BC is usually ER and AR positive, and Luminal-A. MMR loss and PIK3CA mutations are infrequent. Stage and grade predicted overall survival in our South American country population.
A plain language summary of the CAPItello-291 study: Capivasertib in hormone receptor-positive advanced breast cancer
(Taylor and Francis Ltd., 2024) Turner, NC; Oliveira, M; Howell, SJ; Dalenc, F; Cortés, J; Gomez, HL; Hu, X; Jhaveri, K; Krivorotko, P; Loibl, S; Murillo, SM; Park, YH; Sohn, J-H; Toi, M; Tokunaga, E; Yousef, S; Zhukova, L; de, Bruin, E; Grinsted, L; Schiavon, G; Foxley, A; Rugo, HS
What is this summary about?: This is a summary of the article discussing the results of the CAPItello-291 study. In the study, participants had advanced breast cancer that could not be completely removed with surgery, and that was diagnosed as a type of breast cancer where tumor cells had hormone receptors (HR-positive) but did not have HER2 receptors (HER2-negative). All participants were also required to have previously received treatment with a type of therapy called an aromatase inhibitor (with or without a CDK4/6 inhibitor), but over time their cancer cells had still grown or spread. The CAPItello-291 study researchers wanted to find out if a treatment combination of the medications capivasertib plus fulvestrant worked better than placebo plus fulvestrant. Capivasertib is a drug that blocks the activity of a protein called AKT, which is found inside breast cancer cells. What are the key takeaways?: The main finding was that participants who took capivasertib plus fulvestrant lived longer without their disease getting worse (progressing) compared with those treated with placebo plus fulvestrant. This is called progression-free survival. This result was seen across all participants (median progression-free survival of 7.2 months with capivasertib plus fulvestrant vs 3.6 months with placebo plus fulvestrant). It was also seen in participants whose tumors had detectable genetic alterations in genes called PIK3CA, AKT1, and/ or PTEN (median progression-free survival of 7.3 months with capivasertib plus fulvestrant vs 3.1 months with placebo plus fulvestrant). The most common side effects experienced by participants included diarrhea and different types of rash. These were as expected (given how capivasertib works). The CAPItello-291 study is still ongoing, and more results are expected to be released in the future. What were the main conclusions reported by the researchers?: Results from the CAPItello-291 study showed that capivasertib plus fulvestrant compared with placebo plus fulvestrant improved progression-free survival in participants with HR-positive/ HER2-negative advanced breast cancer whose cancer had grown or spread despite hormone therapy (with/without a CDK4/6 inhibitor). Clinical Trial Registration:NCT04305496 (CAPItello-291) (ClinicalTrials.gov).
Adjuvant Pertuzumab and Trastuzumab in Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer in the APHINITY Trial: Third Interim Overall Survival Analysis With Efficacy Update
(Lippincott Williams and Wilkins, 2024) Loibl, S; Jassem, J; Sonnenblick, A; Parlier, D; Winer, E; Bergh, J; Gelber, RD; Restuccia, E; Im, Y-H; Huang, C-S; Dalenc, F; Calvo, I; Procter, M; Caballero, C; Clark, E; Raimbault, A; Mcconnell, R; Monturus, E; De, Azambuja, E; Gomez, HL; Bliss, J; Viale, G; Bines, J; Piccart, M; Aebi, S; Andersson, M; Bonnefoi, H; Cameron, D; Cardoso, F; de, Haas, S; Dent, S; Fein, L; Frank, E; Gnant, M; Gomez, Moreno, H; Im, S-A; Jackisch, C; Janni, W; Krop, I; Kummel, S; Liu, T-W; Loi, S; Masuda, N; Nili, Gam-Yal, E; Nyawira, B; Pascual, T; Pienkowski, T; Rodríguez-Lescure, A; Suter, T; Thomssen, C; Tjan-Heijnen, V; Tomasello, G; Torres, Ulloa, MR; Twelves, C; Walshe, J; Wilcken, N
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. The APHINITY trial (ClinicalTrials.gov identifier: NCT01358877) previously demonstrated that pertuzumab added to adjuvant trastuzumab and chemotherapy improved invasive disease-free survival (iDFS) for patients with early human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC). Here, we report the preplanned third interim analysis of overall survival (OS) and a descriptive updated iDFS analysis with 8.4 years of median follow-up of 4,804 patients in the intent-to-treat population. The 8-year OS was 92.7% in the pertuzumab versus 92.0% in the placebo group (hazard ratio [HR], 0.83 [95% CI, 0.68 to 1.02]; P =.078, above the 0.006 significance threshold). The HR was 0.80 [95% CI 0.63 to 1.00] in the node-positive cohort and 0.99 [95% CI, 0.64 to 1.55] in the node-negative cohort. Updated results of 8-year iDFS in the node-positive cohort showed an absolute improvement of 4.9% favoring pertuzumab (86.1% v 81.2%; HR, 0.72 [95% CI, 0.60 to 0.87]). The node-negative cohort did well without adding pertuzumab (8-year iDFS and OS in the placebo group were 93.3% and 96.4%, respectively). The iDFS benefit was seen in the hormone receptor-negative (HR, 0.82 [95% CI, 0.64 to 1.06]) and HR+ cohorts (HR of 0.75 [95% CI, 0.61 to 0.92]). Despite improvement in overall iDFS, the addition of pertuzumab did not improve OS at this third interim analysis.
Beneficios de la quimioterapia adyuvante en los resultados de supervivencia en cáncer de mama triple negativo PT1N0M0
(Universidad Ricardo Palma, Instituto de Investigaciones en Ciencias Biomedicas, Facultad de Medicina Humana, 2024) Morante, Z; Ferreyra, Y; Valdivieso, N; Castañeda, C; Vidaurre, T; Valencia, G; Otoya, I; Fuentes, H; Neciosup, S; Gomez, HL
Introduction: Triple-negative breast cancer (TNBC) is notably an aggressive breast cancer (BC) subtype, leading to early relapse and poor prognosis. Effects of adjuvant chemotherapy among early-stage TNBC (pT1N0M0) patients remain unclear in different populations. Objectives: Our study aimed to determine the impact of adjuvant chemotherapy on overall survival (OS) and progression-free survival (PFS) within the specific subset of Peruvian pT1N0M0 TNBC patients (pT1a/b vs. pT1c). Methods: We retrospectively analyzed 2007 TNBC cases diagnosed between 2000-2014 at the Instituto Nacional de Enfermedades Neoplásicas (Lima, Peru). We included only non-metastatic TNBC cases and classified them as pT1N0M0 after surgery. TNBC patients who underwent neoadjuvant chemotherapy were excluded. We describe our population according to the tumor size from the residue disease (pT1a/b vs. pT1c). We used the Kaplan-Meier method test to determine differences in survival curves for OS and PFS. A Univariate Cox proportional hazards model was used to identify risk factors for PFS. Results: Our study cohort included 124 TNBC patients. Around 65.3% (n=81) were undergoing adjuvant chemotherapy. Notably, among pT1c patients, this treatment was more prevalent compared to pT1a/b (72.1% vs. 50.0%). Survival analysis showed no significant OS benefit from chemotherapy (HR:2.46,95%CI:0.74-8.13,p=0.13). However, a marked improvement in PFS was noted exclusively in the pT1c subgroup, with patients not treated with chemotherapy offering a prognostic risk (HR:20.10,95% CI:5.54-73.10,p<0.0001). pT1a/b patients demonstrated no benefit from chemotherapy regarding progression (HR:3.07,95% CI:0.27-34.50,p=0.34). Conclusion: Our study highlights that adjuvant chemotherapy significantly improves PFS in pT1cN0M0 TNBC patients but shows no clear benefit for smaller tumors (pT1a/bN0M0). Future research should focus on personalized chemotherapy strategies in early-stage TNBC to identify predictive markers for survival.
Breast cancer subtype and clinical characteristics in women from Peru
(Frontiers Media S.A., 2023) Zavala, VA; Casavilca-Zambrano, S; Navarro-Vasquez, J; Tamayo, LI; Castaneda, CA; Valencia, G; Morante, Z; Calderon, M; Abugattas, JE; Gomez, HL; Fuentes, HA; Liendo-Picoaga, R; Cotrina, JM; Neciosup, SP; Roque, K; Vasquez, J; Mas, L; Galvez-Nino, M; Fejerman, L; Vidaurre, T
Introduction: Breast cancer is a heterogeneous disease, and the distribution of the different subtypes varies by race/ethnic category in the United States and by country. Established breast cancer-associated factors impact subtype-specific risk; however, these included limited or no representation of Latin American diversity. To address this gap in knowledge, we report a description of demographic, reproductive, and lifestyle breast cancer-associated factors by age at diagnosis and disease subtype for The Peruvian Genetics and Genomics of Breast Cancer (PEGEN-BC) study. Methods: The PEGEN-BC study is a hospital-based breast cancer cohort that includes 1943 patients diagnosed at the Instituto Nacional de Enfermedades Neoplásicas in Lima, Peru. Demographic and reproductive information, as well as lifestyle exposures, were collected with a questionnaire. Clinical data, including tumor Hormone Receptor (HR) status and Human Epidermal Growth Factor Receptor 2 (HER2) status, were abstracted from electronic medical records. Differences in proportions and mean values were tested using Chi-squared and one-way ANOVA tests, respectively. Multinomial logistic regression models were used for multivariate association analyses. Results: The distribution of subtypes was 52% HR+HER2-, 19% HR+HER2+, 16% HR-HER2-, and 13% HR-HER2+. Indigenous American (IA) genetic ancestry was higher, and height was lower among individuals with the HR-HER2+ subtype (80% IA vs. 76% overall, p=0.007; 152 cm vs. 153 cm overall, p=0.032, respectively). In multivariate models, IA ancestry was associated with HR-HER2+ subtype (OR=1.38,95%CI=1.06-1.79, p=0.017) and parous women showed increased risk for HR-HER2+ (OR=2.7,95%CI=1.5-4.8, p<0.001) and HR-HER2- tumors (OR=2.4,95%CI=1.5-4.0, p<0.001) compared to nulliparous women. Multiple patient and tumor characteristics differed by age at diagnosis (<50 vs. >=50), including ancestry, region of residence, family history, height, BMI, breastfeeding, parity, and stage at diagnosis (p<0.02 for all variables). Discussion: The characteristics of the PEGEN-BC study participants do not suggest heterogeneity by tumor subtype except for IA genetic ancestry proportion, which has been previously reported. Differences by age at diagnosis were apparent and concordant with what is known about pre- and post-menopausal-specific disease risk factors. Additional studies in Peru should be developed to further understand the main contributors to the specific age of onset and molecular disease subtypes in this population and develop population-appropriate predictive models for prevention. Copyright © 2023 Zavala, Casavilca-Zambrano, Navarro-Vásquez, Tamayo, Castañeda, Valencia, Morante, Calderón, Abugattas, Gómez, Fuentes, Liendo-Picoaga, Cotrina, Neciosup, Roque, Vásquez, Mas, Gálvez-Nino, Fejerman and Vidaurre.
Breast cancer subtype and survival among Indigenous American women in Peru
(Public Library of Science, 2018) Tamayo, LI; Vidaurre, T; Navarro Vásquez, J; Casavilca, S; Aramburu Palomino, JI; Calderon, M; Abugattas Saba, Julio; Gomez, HL; Castaneda, Carlos A; Song, S; Cherry, D; Rauscher, GH; Fejerman, L
Latina women in the U.S. have relatively low breast cancer incidence compared to Non-Latina White (NLW) or African American women but are more likely to be diagnosed with the more aggressive "triple negative" breast cancer (TNBC). Latinos in the U.S. are a heterogeneous group originating from different countries with different cultural and ancestral backgrounds. Little is known about the distribution of tumor subtypes in Latin American regions. Clinical records of 303 female Peruvian patients, from the Peruvian National Cancer Institute, were analyzed. Participants were diagnosed with invasive breast cancer between 2010 and 2015 and were identified as residing in either the Selva or Sierra region. We used Fisher's exact test for proportions and multivariable Cox Proportional Hazards Models to compare overall survival between regions. Women from the Selva region were more likely to be diagnosed with TNBC than women from the Sierra region (31% vs. 14%, p = 0.01). In the unadjusted Cox model, the hazard of mortality was 1.7 times higher in women from the Selva than the Sierra (p = 0.025); this survival difference appeared to be largely explained by differences in the prevalence of TNBC. Our results suggest that the distribution of breast cancer subtypes differs between highly Indigenous American women from two regions of Peru. Disentangling the factors that contribute to this difference will add valuable information to better target prevention and treatment efforts in Peru and improve our understanding of TNBC among all women. This study demonstrates the need for larger datasets of Latin American patients to address differences between Latino subpopulations and optimize targeted prevention and treatment.
Clinicopathological features associated with CD44 and CD63 expression in breast cancer
(ecancer Global Foundation, 2024) Castaneda, CA; Castillo, M; Sanchez, J; Bernabe, L; Tello, K; Suarez, N; Alatrista, R; Quiroz-Gil, X; Granda-Oblitas, A; Enciso, J; Enciso, N; Gomez, HL
Background: CD44 is a cell-surface transmembrane glycoprotein that participates in the regulation of many cellular processes, including cell division, adhesion, migration and stem-like characteristics. CD63 is involved in the exocytosis process. Objective: To evaluate the relationship between CD44 and CD63 expression and clinicopathological features, including tumor-infiltrating lymphocytes (TILs), phosphoinositide 3-kinase (PIK3CA) mutation and survival. Methodology: CD44 and CD63 were stained in samples from 101 breast cancer cases from Peruvian women. Results: Median age was 52 years, most were most were grade-3 (68%), estrogen receptor (ER)+ (64%) and stage II-III (92%). Median ki67 was 30%, median stromal TIL was 30% and PIK3CA mutation was found in 49%. Longer survival was associated with earlier stages (p = 0.016), lower ki67 (p = 0.023), ER+ (p = 0.034), luminal phenotype (p = 0.029) and recurrence (p < 0.001). CD44 was classified as high cell density staining in 57% and high intensity in 55%. High CD44 density was associated with younger age (p = 0.043), triple-negative phenotype (p = 0.035) and shorter survival (p = 0.005). High CD44 expression was associated with short survival (p = 0.005). High CD63 cell density was found in 56% of cases and was associated with ER-positive (p = 0.045), low TIL levels (p = 0.007), Luminal-A (p = 0.015) and low CD44 intensity (p = 0.032). Conclusion: CD44 expression was associated with aggressive features and low CD63 density staining.
Clinicopathological predictors of long-term benefit in breast cancer treated with neoadjuvant chemotherapy
(Baishideng Publishing Group, 2018) Galvez, M; Castaneda, CA; Sanchez, J; Castillo, M; Rebaza, LP; Calderon, G; Cruz, M; Cotrina, JM; Abugattas, J; Dunstan, J; Guerra, H; Mejia, O; Gomez, HL
Aim: To investigate the survival impact of clinicopathological factors, including pathological complete response (pCR) and tumor-infiltrating lymphocytes (sTIL) levels according to subtypes, in breast cancer (BC) patients who received neo-adjuvant chemotherapy (NAC). Methods: We evaluated 435 BC patients who presented and received NAC at the Instituto Nacional de Enfermedades Neoplasicas from 2003 to 2014. sTIL was analyzed as the proportion of tumor stroma occupied by lymphocytes, and was prospectively evaluated on hematoxylin and eosin-stained sections of the preNAC core biopsy. pCR was considered in the absence of infiltrating cancer cells in primary tumor and axillary lymph nodes. Analysis of statistical association between clinical pathological features, sTIL, pCR and survival were carried out using SPSSvs19. Results: Median age was 49 years (range 24-84 years) and the most frequent clinical stage was IIIB (58.3%). Luminal A, Luminal B, HER2-enriched and (triple-negative) TN phenotype was found in 24.6%, 37.9%, 17.7% and 19.8%, respectively. pCR was observed in 11% and median percentage of sTIL was 40% (2%-95%) in the whole population. pCR was associated to Ct1-2 (P = 0.045) and to high sTIL (P = 0.029) in the whole population. There was a slight trend towards significance for sTIL (P = 0.054) in Luminal A. sTIL was associated with grade III (P < 0.001), no-Luminal A subtype (P < 0.001), RE-negative (P < 0.001), PgR-negative (P < 0.001), HER2-positive (P = 0.002) and pCR (P = 0.029) in the whole population. Longer disease-free survival was associated with grade I-II (P = 0.006), cN0 (P < 0.001), clinical stage II (P = 0.004), ER-positive (P < 0.001), PgR-positive (P < 0.001), luminal A (P < 0.001) and pCR (P = 0.002). Longer disease-free survival was associated with grade I-II in Luminal A (P < 0.001), N0-1 in Luminal A (P = 0.045) and TNBC (P = 0.01), clinical stage II in Luminal A (P = 0.003) and TNBC (P = 0.038), and pCR in TNBC (P < 0.001). Longer overall survival was associated with grade I-II (P < 0.001), ER-positive (P < 0.001), PgR-positive (P < 0.001), Luminal A (P < 0.001), cN0 (P = 0.002) and pCR (P = 0.002) in the whole population. Overall survival was associated with clinical stage II (P = 0.017) in Luminal A, older age (P = 0.042) in Luminal B, and pCR in TNBC (P = 0.005). Conclusion: Predictive and prognostic values of clinicopathological features, like pCR and sTIL, differ depending on the evaluated molecular subtype.
Critical review of axillary recurrence in early breast cancer
(Elsevier Ireland Ltd, 2018) Castaneda, Carlos; Rebaza, P; Castillo, Miluska; Gomez, HL; De La Cruz, M; Calderon, G; Dunstan, J; Cotrina, JM; Abugattas, J; Vidaurre, T
Around 2% of early breast cancer cases treated with axillary lymph node dissection (ALND) underwent axillary recurrence (AR) and it has a deleterious effect in prognosis. Different scenarios have incorporated Sentinel Lymph Node (SLN) Biopsy (SLNB) instead of ALND as part of the standard treatment and more effective systemic treatment has also been incorporated in routine management after first curative surgery and after regional recurrence. However, there is concern about the effect of SLNB alone over AR risk and how to predict and treat AR. SLN biopsy (SLNB) has been largely accepted as a valid option for SLN-negative cases, and recent prospective studies have demonstrated that it is also safe for some SLN-positive cases and both scenarios carry low AR rates. Different studies have identified clinicopathological factors related to aggressiveness as well as high-risk molecular signatures can predict the development of locoregional recurrence. Other publications have evaluated factors affecting prognosis after AR and find that time between initial treatment and AR as well as tumor aggressive behavior influence patient survival. Retrospective and prospective studies indicate that treatment of AR should include local and systemic treatment for a limited time.
Effect of CCL5 expression in the recruitment of immune cells in triple negative breast cancer
(Nature Publishing Group, 2018) Araujo, JM; Gomez, AC; Aguilar, A; Salgado, R; Balko, JM; Bravo, L; Doimi, F; Bretel, D; Morante, Z; Flores, C; Gomez, HL; Pinto, JA
Triple negative breast cancer (TNBC) is the most aggressive form of breast cancer with limited options of targeted therapy. Recent findings suggest that the clinical course of TNBC may be modified by the presence of tumor-infiltrating lymphocytes (TILs) and chemokine's expression, such as CCL5. Diverse studies have shown that CCL5 suppresses anti-tumor immunity and it has been related to poor outcome in different types of cancer while in other studies, this gene has been related with a better outcome. We sought to determine the association of CCL5 with the recruitment of TILs and other immune cells. With this aim we evaluated a retrospective cohort of 72 TNBC patients as well as publicly available datasets. TILs were correlated with residual tumor size after neoadjuvant chemotherapy (NAC) and CCL5 expression. In univariate analysis, TILs and CCL5 were both associated to the distant recurrence free survival; however, in a multivariate analysis, TILs was the only significant marker (HR = 0.336; 95%IC: 0.150-0.753; P = 0.008). CIBERSORT analysis suggested that a high CCL5 expression was associated with recruitment of CD8 T cells, CD4 activated T cells, NK activated cells and macrophages M1. The CD8A gene (encoding for CD8) was associated with an improved outcome in several public breast cancer datasets.
End-of-neoadjuvant treatment circulating microRNAs and HER2-positive breast cancer patient prognosis: An exploratory analysis from NeoALTTO
(Frontiers Media S.A., 2023) Di-Cosimo, S; Ciniselli, CM; Pizzamiglio, S; Cappelletti, V; Silvestri, M; El-Abed, S; Izquierdo, M; Bajji, M; Nuciforo, P; Huober, J; Cameron, D; Chia, S; Gomez, HL; Iorio, MV; Vingiani, A; Pruneri, G; Verderio, P
Background: The absence of breast cancer cells in surgical specimens, i.e., pathological complete response (pCR), is widely recognized as a favorable prognostic factor after neoadjuvant therapy. In contrast, the presence of disease at surgery characterizes a prognostically heterogeneous group of patients. Here, we challenged circulating microRNAs (miRNAs) at the end of neoadjuvant therapy as potential prognostic biomarkers in the NeoALTTO study. Methods: Patients treated within the trastuzumab arm (i.e., pre-operative weekly trastuzumab for 6 weeks followed by the addition of weekly paclitaxel for 12 weeks; post-operative FEC for 3 cycles followed by trastuzumab up to complete 1 year of treatment) were randomized into a training (n= 54) and testing (n= 72) set. RT-PCR-based high-throughput miRNA profile was performed on plasma samples collected at the end of neoadjuvant treatment of both sets. After normalization, circulating miRNAs associated with event free survival (EFS) were identified by univariate and multivariate Cox regression model. Results: Starting from 23 circulating miRNAs associated with EFS in the training set, we generated a 3-circulating miRNA prognostic signature consisting of miR-185-5p, miR-146a-5p, miR-22-3p, which was confirmed in the testing set. The 3-circulating miRNA signature showed a C-statistic of 0.62 (95% confidence interval [95%CI] 0.53-0.71) in the entire study cohort. By resorting to a multivariate Cox regression model we found a statistical significant interaction between the expression values of miR-194-5p and pCR status (p.interaction =0.005) with an estimate Hazard Ratio (HR) of 1.83 (95%CI 1.14- 2.95) in patients with pCR, and 0.87 (95%CI 0.69-1.10) in those without pCR. Notably, the model including this interaction along with the abovementioned 3-circulating miRNA signature provided the highest discriminatory capability with a C-statistic of 0.67 (95%CI 0.58-0.76). Conclusions: Circulating miRNAs are informative to identify patients with different prognosis among those with heterogeneous response after trastuzumab-based neoadjuvant treatment, and may be an exploitable tool to select candidates for salvage adjuvant therapy. Copyright © 2023 Di Cosimo, Ciniselli, Pizzamiglio, Cappelletti, Silvestri, El-Abed, Izquierdo, Bajji, Nuciforo, Huober, Cameron, Chia, Gomez, Iorio, Vingiani, Pruneri and Verderio.
First-Line (1L) Treatment Decision Patterns and Survival of Hormone Receptor (HR)-Positive/HER2-Negative Advanced Breast Cancer (ABC) Patients in a Latin American (LATAM) Public Institution
(Multidisciplinary Digital Publishing Institute (MDPI), 2024) Valencia, G; Rioja, P; Chirito, M; Peralta, O; Sánchez, J; Rabanal, C; Mantilla, R; Morante, Z; Fuentes, H; Castaneda, C; Vidaurre, T; Pacheco, C; Neciosup, S; Gomez, HL
Advanced breast cancer is an incurable disease, with a median overall survival of 3 years, including in countries without access problems. Although chemotherapy is reserved in some cases, it is still used in many countries as a first-line therapy. The aim of our study is to evaluate the first-line treatment choices and the factors that influence therapeutic decisions. A retrospective analysis was conducted of hormone receptor (+)/HER2 (−) advanced breast cancer patients classified into three groups according to the first-line and second-line treatment received: endocrine therapy–chemotherapy, endocrine therapy–endocrine therapy and chemotherapy–endocrine therapy. Additionally, we explored the overall survival of sequencing therapy groups. First-line chemotherapy was chosen in 34% of patients. Also, around 60% of our patients met the “aggressive disease” criteria from the RIGHT Choice trial, justifying the use of chemotherapy in a population with poor prognosis. Furthermore, de novo and progressive disease were prognostic factors that influenced the use of chemotherapy as a first-line treatment. Regarding overall survival, the sequencing treatment groups in this trial saw an increase in survival compared with patients of the MONALEESA trials (endocrine therapy alone arms). No significant differences in progression-free survival or overall survival were found in the treatment sequencing groups. There was a higher use of chemotherapy as a first-line therapy, with de novo and “aggressive disease” criteria being the main factors to influence the decision.
Implication of miRNA in the diagnosis and treatment of breast cancer
(Taylor and Francis Ltd., 2011) Castañeda, CA; Agullo-Ortuño, MT; Fresno Vara, JA; Cortes-Funes, H; Gomez, HL; Ciruelos, E
Breast cancer (BC) comprises a group of different diseases characterized by changes in tissue structure and gene expression. Recent advances in molecular biology have shed new light on the participation of genes and their products in the biology of BC. MicroRNAs (miRNAs) are small noncoding endogenous RNA molecules that appear to modulate the expression of more than a third of human genes, and their implications in cancer have grasped the attention of the scientific community. Recently, several studies have described the association between miRNA expression profiles and pathological and clinical BC features. Moreover, these molecules represent a new type of molecular marker that can identify prognosis and guide the management of BC patients. With the increasing understanding of miRNA networks and their impact in the biology of BC, as well as the development of viable strategies to modulate specific miRNAs, we could improve the treatment of this disease.
Knowledge, attitudes, and behaviors toward fertility preservation in patients with breast cancer: A cross-sectional survey of physicians
(Frontiers Media S.A., 2023) Baek, SY; Lee, KH; Kim, SB; Gomez, HL; Vidaurre, T; Park, YH; Ahn, HK; Kim, YS; Park, IH; Ahn, SG; Lee, J; Jeong, JH; Kim, S; Kim, HJ
Background: Fertility is an important issue for young women with breast cancer, but studies about physicians’ knowledge, attitudes, and practices toward fertility preservation (FP) are largely based on Western populations and do not reflect recent international guidelines for FP. In this international study, we aimed to assess the knowledge, attitudes, and practices of physicians from South Korea, other Asian countries, and Latin America toward FP in young women with breast cancer, and identify the related barriers. Methods: The survey was conducted anonymously among physicians from South Korea, other Asian countries, and Latin America involved in breast cancer care between November 2020 and July 2021. Topics included knowledge, attitudes, and perceptions toward FP; practice behaviors; barriers; and participant demographics. We grouped related questions around two main themes—discussion with patients about FP, and consultation and referral to a reproductive endocrinologist. We analyzed the relationships between main questions and other survey items. Results: A total of 151 physicians completed the survey. Most participants’ overall knowledge about FP was good. More than half of the participants answered that they discussed FP with their patients in most cases, but that personnel to facilitate discussions about FP and the provision of educational materials were limited. A major barrier was time constraints in the clinic (52.6%). Discussion, consultations, and referrals were more likely to be performed by surgeons who primarily treated patients with operable breast cancer (FP discussion odds ratio [OR]: 2.90; 95% confidence interval [CI]: 1.24–6.79; FP consultation and referral OR: 2.98; 95% CI: 1.14–7.74). Participants’ knowledge and attitudes about FP were significantly associated with discussion, consultations, and referrals. Conclusion: Physicians from South Korea, other Asian countries, and Latin America are knowledgeable about FP and most perform practice behaviors toward FP well. Physicians’ knowledge and favorable attitudes are significantly related to discussion with patients, as well as consultation with and referral to reproductive endocrinologists. However, there are also barriers, such as limitations to human resources and materials, suggesting a need for a systematic approach to improve FP for young women with breast cancer.
Low-Dose Oral Cyclophosphamide and Methotrexate Maintenance for Hormone Receptor-Negative Early Breast Cancer: International Breast Cancer Study Group Trial 22-00
(American Society of Clinical Oncology, 2017) Colleoni, M; Gray, KP; Gelber,S; Láng, I; Thürlimann, B; Gianni, L; Abdi, EA; Gomez, HL; inderholm, BK; Puglis,i F; Tondini, C; Kralidis, E; Eniu, A; Cagossi, K; Rauch, D; Chirgwin, J; Gelber, RD; Regan, MM; Coates, AS; Price, KN; Viale, G; Goldhirsch, A
Purpose: To evaluate the benefit of low-dose cyclophosphamide and methotrexate (CM) maintenance, which previously demonstrated antitumor activity and few adverse effects in advanced breast cancer, in early breast cancer. Patients and methods: International Breast Cancer Study Group (IBCSG) Trial 22-00, a randomized phase III clinical trial, enrolled 1,086 women (1,081 intent-to-treat) from November 2000 to December 2012. Women with estrogen receptor- and progesterone receptor-negative (< 10% positive cells by immunohistochemistry) early breast cancer any nodal and human epidermal growth factor receptor 2 status, were randomly assigned anytime between primary surgery and 56 days after the first day of last course of adjuvant chemotherapy to CM maintenance (cyclophosphamide 50 mg/day orally continuously and methotrexate 2.5 mg twice/day orally on days 1 and 2 of every week for 1 year) or to no CM. The primary end point was disease-free survival (DFS), which included invasive recurrences, second (breast and nonbreast) malignancies, and deaths. Results: After a median of 6.9 years of follow-up, DFS was not significantly better for patients assigned to CM maintenance compared with patients assigned to no CM, both overall (hazard ratio [HR], 0.84; 95% CI, 0.66 to 1.06;P = .14) and in triple-negative (TN) disease (n = 814; HR, 0.80; 95% CI, 0.60 to 1.06). Patients with TN, node-positive disease had a nonstatistically significant reduced HR (n = 340; HR, 0.72; 95% CI, 0.49 to 1.05). Seventy-one (13%) of 542 patients assigned to CM maintenance did not start CM. Of 473 patients who received at least one CM maintenance dose (including two patients assigned to no CM), 64 (14%) experienced a grade 3 or 4 treatment-related adverse event; elevated serum transaminases was the most frequently reported (7%), followed by leukopenia (2%). Conclusion: CM maintenance did not produce a significant reduction in DFS events in hormone receptor-negative early breast cancer. The trend toward benefit observed in the TN, node-positive subgroup supports additional exploration of this strategy in the TN, higher-risk population.
Pathological Response in a Triple-Negative Breast Cancer Cohort Treated with Neoadjuvant Carboplatin and Docetaxel According to Lehmann's Refined Classification
(American Association for Cancer Research Inc., 2018) Echavarria, I; López-Tarruella, S; Picornell, A; García-Saenz, JÁ; Jerez, Y; Hoadley, K; Gomez, HL; Moreno, F; Monte-Millan, MD; Márquez-Rodas, I; Alvarez, E; Ramos-Medina, R; Gayarre, J; Massarrah, T; Ocaña, I; Cebollero, M; Fuentes, H; Barnadas, A; Ballesteros, AI; Bohn, U; Perou, CM; Martin, M
Purpose: Triple-negative breast cancer (TNBC) requires the iden- tification of reliable predictors of response to neoadjuvant chemotherapy (NACT). For this purpose, we aimed to evaluate the performance of the TNBCtype-4 classifier in a cohort of patients with TNBC treated with neoadjuvant carboplatin and docetaxel (TCb).Methods: Patients with TNBC were accrued in a nonrandomized trial of neoadjuvant carboplatin AUC 6 and docetaxel 75 mg/m2 for six cycles. Response was evaluated in terms of pathologic complete response (pCR, ypT0/is ypN0) and residual cancer burden by Symmans and colleagues. Lehmann's subtyping was performed using the TNBCtype online tool from RNAseq data, and germline sequencing of a panel of seven DNA damage repair genes was conducted.Results: Ninety-four out of the 121 patients enrolled in the trial had RNAseq available. The overall pCR rate was 44.7%. Lehmann subtype distribution was 34.0% BL1, 20.2% BL2, 23.4% M, 14.9% LAR, and 7.4% were classified as ER+. Response to NACT with TCb was significantly associated with Lehmann subtype (P = 0.027), even in multivariate analysis including tumor size and nodal involvement, with BL1 patients achieving the highest pCR rate (65.6%), followed by BL2 (47.4%), M (36.4%), and LAR (21.4%). BL1 was associated with a significant younger age at diagnosis and higher ki67 values. Among our 10 germline mutation carriers, 30% were BL1, 40% were BL2, and 30% were M.Conclusions: TNBCtype-4 is associated with significantly different pCR rates for the different subtypes, with BL1 and LAR displaying the best and worse responses to NACT, respectively. Clin Cancer Res; 24(8); 1845-52. ©2018 AACR.
Practice-Changing Use of the 21-Gene Test for the Management of Patients With Early-Stage Breast Cancer in Latin America
(American Society of Clinical Oncology, 2021) Gomez, HL; Bargallo-Rocha, JE; Billinghurst, RJ; Núñez De Pierro, AR; Coló, FA; Gil, LL; Allemand, C; McLean, IL; Lema-Medina, M; Herazo-Maya; Terrier, FJ; Cwilich, RG; Leon, M; Falcon, SG; Castaño, RE; Oliveira, SC; Jakubowski, DM; Chao, C
Purpose: We present a physician survey of the impact of 21-gene Breast Recurrence Score test results on treatment decisions in clinical practice in Latin America.Methods: This prospective survey enrolled consecutive patients at 14 sites in Argentina, Colombia, Mexico, and Peru who had routine 21-gene testing. Physician surveys captured patient and tumor characteristics and treatment decisions before and after 21-gene test results. The survey spanned the period before and after Trial Assigning Individualized Options for Treatment (TAILORx) results reported (June 2018). Overall net percent change in adjuvant chemotherapy recommendations was estimated, and asymptotic 95% CIs with continuity correction were calculated. The proportion with a change between pretest treatment recommendation and actual treatment received was calculated overall and by Recurrence Score groups per TAILORx.Results: Between March 2015 and December 2019, the survey was completed for 647 patients; 20% were node-positive. The mean patient age was 54 years (24-85 years); 55% were postmenopausal; 17%, 63%, and 20% had grade 1, 2, and 3 tumors, respectively; and 30% had tumors > 2 cm. Recurrence Score (RS) results were as follows: 20% RS 0-10, 56% RS 11-25, and 24% RS 26-100. Overall, chemotherapy recommendations fell by a relative proportion of 39% (95% CI, 33.4 to 44.3) after 21-gene testing (33% decrease in node-negative and 55% decrease in node-positive). Among node-negative patients, the relative decrease in chemotherapy recommendations was 28% (95% CI, 18.9 to 39.5) before TAILORx and 36% (95% CI, 28.4 to 43.7) after.Conclusion: To our knowledge, this large survey of 21-gene test practice patterns was the first conducted in Latin America and showed the relevance of 21-gene testing in low- and medium-resource countries to minimize chemotherapy overuse and underuse in breast cancer. The results showed substantial reductions in chemotherapy use overall-especially after TAILORx reported-indicating the practice-changing potential of that study.
Prognostic factors for patients with newly diagnosed brain metastasis from breast cancer
(Future Medicine Ltd., 2015) Castaneda, Carlos; Flores, R; Castillo, Miluska; Rojas, KY; Castillo, M; Dolores-Cerna, K; Flores, C; Belmar-Lopez, C; Milla, E; Gomez, HL
Aim: This retrospective study determined features associated with brain metastasis (BM) in women with breast cancer. Patients & methods: A total of 215 initially early breast cancer cases were included. We reviewed files and CT scan images of BM. Results: Median age was 47 years and most of our cases were stage III (58.6%), grade III (62.8%), ER negative (62.3%) and nonluminal (59.1%). Median survival after BM was 4 months. Nonluminal, extracranial disease, time to CNS shorter than 15 months, >three brain lesions and poor breast-graded prognostic assessment and recursive partitioning analysis scores were associated with shorter survival. Adding extracranial disease to breast-graded prognostic assessment score also predicted survival after BM. Radiation response was assessed in 57 patients and response tended to be associated with nonluminal phenotype but not with survival. Conclusion: Factors associated with both initial tumor and clinical features at BM time are associated with shorter survival in our Latinas population.
Prospective Validation of a 21-Gene Expression Assay in Breast Cancer
(Massachussetts Medical Society, 2015) Sparano, JA; Gray, RJ; Makower, DF; Pritchard, KI; Albain, KS; Hayes, DF; Geyer, CE Jr; Dees, EC; Perez, EA; Olson, JA Jr; Zujewski, J; Lively, T; Badve, SS; Saphner, TJ; Wagner, LI; Whelan, TJ; Ellis, MJ; Paik, S; Wood, WC; Ravdin, P; Keane, MM; Gomez, HL; Reddy, PS; Goggins, TF; Mayer, IA; Brufsky, AM; Toppmeyer, DL; Kaklamani, VG; Atkins, JN; Berenberg, JL; Sledge, GW
Prior studies with the use of a prospective–retrospective design including archival tumor samples have shown that gene-expression assays provide clinically useful prognostic information. However, a prospectively conducted study in a uniformly treated population provides the highest level of evidence supporting the clinical validity and usefulness of a biomarker.
Race, Ethnicity, and Clinical Outcomes in Hormone Receptor-Positive, HER2-Negative, Node-Negative Breast Cancer in the Randomized TAILORx Trial
(Oxford University Press, 2021) Albain, KS; Gray, RJ; Makower, DF; Faghih, A; Hayes, DF; Geyer, CE; Dees, EC; Goetz, MP; Olson, JA; Lively, T; Badve, SS; Saphner, TJ; Wagner, LI; Whelan, TJ; Ellis, MJ; Wood, WC; Keane, MM; Gomez, HL; Reddy, PS; Goggins, TF; Mayer, IA; Brufsky, AM; Toppmeyer,DL; Kaklamani, VG; Berenberg, JL; Abrams, J; Sledge, GW; Sparano, JA
Background: Black race is associated with worse outcomes in early breast cancer. We evaluated clinicopathologic characteristics, the 21-gene recurrence score (RS), treatment delivered, and clinical outcomes by race and ethnicity among women who participated in the Trial Assigning Individualized Options for Treatment. Methods: The association between clinical outcomes and race (White, Black, Asian, other or unknown) and ethnicity (Hispanic vs non-Hispanic) was examined using proportional hazards models. All P values are 2-sided. Results: Of 9719 eligible women with hormone receptor-positive, HER2-negative, node-negative breast cancer, there were 8189 (84.3%) Whites, 693 (7.1%) Blacks, 405 (4.2%) Asians, and 432 (4.4%) with other or unknown race. Regarding ethnicity, 889 (9.1%) were Hispanic. There were no substantial differences in RS or ESR1, PGR, or HER2 RNA expression by race or ethnicity. After adjustment for other covariates, compared with White race, Black race was associated with higher distant recurrence rates (hazard ratio [HR] = 1.60, 95% confidence intervals [CI] = 1.07 to 2.41) and worse overall survival in the RS 11-25 cohort (HR = 1.51, 95% CI = 1.06 to 2.15) and entire population (HR = 1.41, 95% CI = 1.05 to 1.90). Hispanic ethnicity and Asian race were associated with better outcomes. There was no evidence of chemotherapy benefit for any racial or ethnic group in those with a RS of 11-25. Conclusions: Black women had worse clinical outcomes despite similar 21-gene assay RS results and comparable systemic therapy in the Trial Assigning Individualized Options for Treatment. Similar to Whites, Black women did not benefit from adjuvant chemotherapy if the 21-gene RS was 11-25. Further research is required to elucidate the basis for this racial disparity in prognosis.