Paula Cabrera-Galeana

Purpose: Breast cancer (BC) is the most common malignancy in women and a leading cause of cancer-related mortality in Latin America (LATAM). This region is characterized by marked disparities in incidence, mortality, and care delivery, yet these differences have not been systematically examined. Methods: The LATINA study is a multinational, prospective cohort design to characterize BC in LATAM, enrolling patients 18 years and older with newly diagnosed BC across 10 countries. Data collection occurred at baseline and every 6 months for up to 5 years postenrollment. Multivariable logistic regression was used to identify associations between advanced-stage diagnosis and the detection method. Causal mediation analysis evaluated whether the detection method mediated the association between the type of health care coverage (public v private) and the stage at diagnosis. Results: Among 3,275 patients, 72.1% received care in public health systems and 41.8% were 50 years and younger. Overall, 40.5% presented at an advanced stage (III or IV). The most common molecular subtypes were luminal A (41.3%) and human epidermal growth factor receptor 2 (HER2)–positive (22.9%). Most patients were diagnosed based on symptoms (60.3%). Symptom-detected disease was more frequent among patients in the public health system (68.3% v 59.6% private; P < .001). In multivariable analyses, younger age (≤40 years), public health care coverage, symptom-detected disease, and HER2 overexpression were independently associated with advanced-stage presentation. Younger age, Black or African American/Brown race, public health care coverage, lower educational attainment, unemployment, unmarried status, and triple-negative disease were associated with symptom-detected diagnosis. Conclusion: A substantial proportion of BC cases in LATAM are diagnosed symptomatically and at advanced stages. Late-stage presentation is associated with sociodemographic characteristics and type of health care coverage. Strategies that expand screening programs and strengthen early diagnosis will be essential to improve early detection and reduce disparities in BC outcomes across LATAM.

Background: Triple-negative breast cancer (TNBC) is a biologically heterogeneous, aggressive disease where immunohistochemistry (IHC)-based algorithms, defining luminal androgen receptor (LAR), immunomodulatory (IM), basal-like immunosuppressed (BLIS), mesenchymal (MES), and unclassifiable (UC) subtypes, offer a pragmatic alternative to transcriptomics. This study evaluated clinical trajectories and survival outcomes associated with IHC-based molecular subtypes and stromal tumor-infiltrating lymphocytes (sTILs) across distinct subgroups. Methods: A retrospective analysis of 289 women with TNBC treated with chemotherapy-only regimens analyzed molecular subtypes across four clinical groups: non-recurrent, recurrent, progression during neoadjuvant chemotherapy, and de novo metastatic disease. IHC-based subclassification included androgen receptor (AR), CD8, FOXC1, and DCLK1 biomarkers. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method, and multivariable Cox proportional hazards models. Results: The cohort included non-recurrent (43.9%), recurrent (26.3%), neoadjuvant progressors (11.5%), and de novo stage IV (18.3%) cases. IM subtype (16.3%) was enriched in non-recurrent cases with the highest median sTILs levels (20.0%). BLIS (26.3%) and UC (39.4%) subtypes predominated in recurrent and metastatic disease, while MES subtype (9.0%) predominated in neoadjuvant chemotherapy progressors. In early-stage disease, sTILs ≥10% independently predicted superior OS (HR 0.63, 95% CI, 0.40-1.0; P = .049), showing no prognostic role in the de novo stage IV group. Molecular subtypes lost independent significance in multivariable models. Conclusions: Clinicopathological factors and sTILs remain primary prognostic determinants in TNBC. Although IHC-based molecular subtypes were not independent survival predictors, their differential clinical distribution validates their biological relevance to identify therapeutic vulnerabilities, and to guide precision medicine and de-escalation strategies.

Central nervous system (CNS) metastases are a frequent and ominous scenario in patients with breast cancer. CNS metastases (CNSm) are typically classified as brain metastases (BrMs) or leptomeningeal disease (LMD). Although the coexistence of BrMs and LMD (BrMs + LMD) is commonly encountered in clinical practice, its true prevalence and prognostic implications remain insufficiently characterized. This study aimed to characterize the distribution of CNSm and compare outcomes in patients with breast cancer BrMs with and without LMD. We retrospectively analyzed a prospectively maintained database of patients with breast cancer and magnetic resonance imaging (MRI)-confirmed CNSm treated at a single tertiary cancer center between January 2010 and January 2023. Among 659 patients with breast cancer CNSm, 292 (44%) had BrMs, 169 (26%) had LMD, and 198 (30%) had BrMs + LMD. The CNSm survival for the entire cohort was 9.6 months (95% CI, 8.0-11.2); 12.2 months (95% CI, 9.9-14.5) in the BrMs group; 5.8 months (95% CI, 4.3-7.2) in the LMD group; and 10.3 months (95% CI, 8.0-12.7 months) in the BrMs + LMD group (P < 0.001). After adjustment for performance status, number of brain metastases, and molecular subtype, the risk of mortality remained higher in the BrMs + LMD group (HR 1.24; 95% CI, 1.01-1.52; P = 0.032) compared with the BrMs group. In patients with breast cancer and brain metastases, concomitant leptomeningeal involvement is common and independently associated with worse survival. These findings support the need to incorporate leptomeningeal disease status into prognostic models and clinical decision-making for CNSm in patients with breast cancer.

Background: Young women with breast cancer (YWBC) face medical and psychosocial challenges that are inconsistently addressed by healthcare frameworks. This study evaluated whether a patient navigation (PN) program for YWBC facilitates access to specialty and supportive care through structured patient needs assessments and referrals. Patients and Methods: Within 3 months of diagnosis, ≤40-year-old patients were prospectively enrolled into a PN program in which a navigator systematically administered needs detection surveys and provided referrals to required services at baseline, 3 months (m), and 6 m. Attendance to referrals at baseline and 3 m was assessed at the next timepoint. Results: Among 189 participants, 85% required >2 referrals at any timepoint. At baseline and 3 m, referrals were mostly to nutrition (66% and 46%), support groups (65% and 24%), and psychology (56% and 36%); and at 6 m, to nutrition (32%), sexology (31%), and psychology (19%). From baseline-to-3m, attendance was highest for support groups (99%), genetic cancer risk assessment (88%), and external breast prosthesis providers (82%); from 3 m-to-6m, for support groups (100%), sexology (91%), and external breast prosthesis (86%). Nearly none attended >2 referrals and receiving more referrals was associated with higher absence rates (p<.001). Conclusion: This PN program enabled structured identification of patients’ needs and referral to required services, highlighting the relevance of nutrition, support groups, and psychology needs during early assessments, as well as sexology counseling during later follow-ups. The high absence rates observed suggest that individualized selection of specific referrals prioritizing patients’ needs and preferences at different timepoints in their cancer trajectory could improve attendance while avoiding patient and health-system oversaturation.

PURPOSE: Breast cancer is a significant public health issue worldwide, with a particularly high impact in Latin America (LATAM). Genetic risk assessment and germline molecular testing for pathogenic variants in actionable genes are established practices for managing breast cancer risk. Cascade testing, genetic testing of at-risk relatives of individuals carrying these variants, provides a pivotal strategy for cancer prevention and early detection. DESIGN: This review examines the status of cascade testing among patients with breast cancer in LATAM, highlighting the barriers to its implementation and identifying opportunities to expand its application in the region. RESULTS: Despite growing awareness of the importance of genetic risk assessment, the adoption of cascade testing remains limited in LATAM. Key barriers include restricted access to genetic services, financial and infrastructural limitations within public health systems, and sociocultural factors. However, locally driven initiatives that integrate genetic counseling into national health systems and emphasize education for health care providers have demonstrated the potential to foster long-term sustainability. The role of artificial intelligence and machine learning in genetic counseling is emerging, offering possible solutions to optimize cascade testing, but further evidence is required to assess their impact across diverse populations. CONCLUSION: The successful integration of cascade testing into Latin American health care systems requires strategies rooted in local initiatives, supported by public policies, and driven by health care professionals committed to changing paradigms in cancer prevention. Sustainable approaches should prioritize capacity-building, equitable access to genetic services, and the empowerment of health care providers to recognize the transformative impact of genetic counseling on patient outcomes. By fostering regionally adapted models, LATAM can enhance hereditary cancer prevention and ultimately reduce breast cancer incidence and mortality.

Cutaneous manifestations can serve as early and sometimes the first clinical indicators in various hereditary cancer predisposition syndromes. This review provides a comprehensive overview of the dermatological signs associated with these syndromes, aiming to facilitate their recognition in clinical practice. Hereditary Breast and Ovarian Cancer syndrome is notably linked to an increased risk of melanoma. BAP1 tumor predisposition syndrome is characterized by BAP1-inactivated melanocytic tumors. Muir–Torre syndrome, a variant of Lynch syndrome, presents with distinctive cutaneous neoplasms such as sebaceous carcinomas, sebaceous adenomas, and keratoacanthomas. PTEN hamartoma tumor syndrome commonly features hamartomatous growths, trichilemmomas, acral keratoses, oral papillomas, and genital lentiginosis. Gorlin syndrome is marked by basal cell carcinomas and palmoplantar pits, while Peutz–Jeghers syndrome is identified by mucocutaneous pigmentation. In familial adenomatous polyposis, the cutaneous findings include epidermoid cysts, fibromas, desmoid tumors, and lipomas. Additionally, we examined monogenic disorders associated with cancer risk and skin involvement, such as xeroderma pigmentosum, neurofibromatosis type 1, familial atypical multiple-mole melanoma syndrome, and Fanconi anemia. The early recognition of these dermatologic features is essential for a timely diagnosis and the implementation of appropriate surveillance strategies in individuals with hereditary cancer syndromes.

Young women with breast cancer (YWBC) face unique challenges that can impact their sexual health. This study aimed to identify factors associated with sexual activity, function, and satisfaction in YWBC up to five years post-diagnosis. We conducted a prospective cohort study of 474 women aged ≤40 years diagnosed with non-metastatic breast cancer in Mexico. Sexual function and satisfaction were assessed using the Female Sexual Function Index and the Sexual Satisfaction Inventory, respectively. Factors associated with sexual health outcomes were examined using mixed-effects models. The prevalence of sexual dysfunction increased from 33.6% at baseline to 52.9% at 4-5 years post-diagnosis. Factors associated with worse sexual function included older age (mean predicted FSFI score -1.35, p = .037), treatment-induced amenorrhea (-2.86, p < .001), depression (-4.11, p < .001), and anxiety (-2.13, p < .001). Lower sexual satisfaction was associated with lower educational attainment (mean predicted SSI score -5.61, p = .002), being single (-6.41, p < .001), treatment induced amenorrhea (-3.76, p = .004), bilateral oophorectomy (-8.21, p = .017), depression (-11.29, p < .001), and anxiety (-7.50, p < .001). Quality of life, body image, and systemic therapy side effects significantly impacted both outcomes. Three distinct trajectories of sexual function were identified: high (62.2%), intermediate (24.3%), and markedly declining (13.5%). Four trajectories of sexual satisfaction were found, ranging from intermediate-to-high (57.3%) to progressively worsening (27.5%). Sexual dysfunction is prevalent and persistent among YWBC. Multiple biological, psychological, and social factors influence sexual health outcomes in this population. These findings highlight the importance of routine screening and tailored interventions to address the sexual health of YWBC throughout survivorship.

Purpose Breast cancer is the most prevalent cancer type in Mexico, with male breast cancer accounting for only 1% of all breast cancer cases. A limited number of studies have described the clinical-pathological profiles of males with breast cancer in low- and middle-income countries. This study presents an analysis of patients with breast cancer seen at three different institutions in México. Methods A retrospective review of the medical records was performed to analyze the clinical and pathological characteristics of 49 men diagnosed with breast cancer and their overall survival. Results The mean age at diagnosis was 64.65 years. A significant proportion of patients presented at diagnosis with stage IV disease (n = 11, 22.45%), had triple-negative subtype (n = 6, 12.24%), and nuclear grade III (n = 20, 40.8%). Primary endocrine resistance was observed in 10 patients (31.25%). Genetic analysis was performed on 24 patients (48.9%), revealing a germline BRCA pathogenic variant in 8.33%. Conclusion Our findings described the clinical and pathological profile of breast cancer in a male cohort in Mexico, with a significantly high proportion of advanced disease, triple-negative subtype, nuclear grade III, and endocrine resistance. Further comprehensive studies, including research into somatic mutations, are needed.

LncRNAs are noncoding transcripts with tissue and cancer specificity. Particularly, in breast cancer, lncRNAs exhibit subtype-specific expression; they are particularly upregulated in luminal tumors. However, no gene signature-based laboratory tests have been developed for luminal breast cancer identification or the differential diagnosis of luminal tumors, since no luminal A- or B-specific genes have been identified. Particularly, luminal B patients are of clinical interest, since they have the most variable response to neoadjuvant treatment; thus, it is necessary to develop diagnostic and predictive biomarkers for these patients to optimize treatment decision-making and improve treatment quality. In this study, we analyzed the lncRNA expression profiles of breast cancer cell lines and patient tumor samples from RNA-Seq data to identify an lncRNA signature specific for luminal phenotypes. We identified an lncRNA signature consisting of LINC01016, GATA3-AS1, MAPT-IT1, and DSCAM-AS1 that exhibits luminal subtype-specific expression; among these lncRNAs, GATA3-AS1 is associated with the presence of residual disease (Wilcoxon test, p < 0.05), which is related to neoadjuvant chemotherapy resistance in luminal B breast cancer patients. Furthermore, analysis of GATA3-AS1 expression using RNA in situ hybridization (RNA ISH) demonstrated that this lncRNA is detectable in histological slides. Similar to estrogen receptors and Ki67, both commonly detected biomarkers, GATA3-AS1 proves to be a suitable predictive biomarker for clinical application in breast cancer laboratory tests.