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Background: Breast cancer (BC) in women aged ≤40 years carrying germline pathogenetic variants (PVs) in BRCA1/2 genes is infrequent but often associated with aggressive features. Human epidermal growth factor receptor 2 (HER2)-low-expressing BC has recently emerged as a novel therapeutic target but has not been characterized in this rare patient subset., Methods: Women aged ≤40 years with newly diagnosed early-stage HER2-negative BC (HER2-0 and HER2-low) and germline BRCA1/2 PVs from 78 health care centers worldwide were retrospectively included. Chi-square test and Student t-test were used to describe variable distribution between HER2-0 and HER2-low. Associations with HER2-low status were assessed with logistic regression. Kaplan-Meier method and Cox regression analysis were used to assess disease-free survival (DFS) and overall survival. Statistical significance was considered for p ≤ .05., Results: Of 3547 included patients, 32.3% had HER2-low BC, representing 46.3% of hormone receptor-positive and 21.3% of triple-negative (TN) tumors. HER2-low vs. HER2-0 BC were more often of grade 1/2 (p < .001), hormone receptor-positive (p < .001), and node-positive (p = .003). BRCA2 PVs were more often associated with HER2-low than BRCA1 PVs (p < .001). HER2-low versus HER2-0 showed better DFS (hazard ratio [HR], 0.86; 95% CI, 0.76-0.97) in the overall population and more favorable DFS (HR, 0.78; 95% CI, 0.64-0.95) and overall survival (HR, 0.65; 95% CI, 0.46-0.93) in the TN subgroup. Luminal A-like tumors in HER2-low (p = .014) and TN and luminal A-like in HER2-0 (p = .019) showed the worst DFS., Conclusions: In young patients with HER2-negative BC and germline BRCA1/2 PVs, HER2-low disease was less frequent than expected and more frequently linked to BRCA2 PVs and associated with luminal-like disease. HER2-low status was associated with a modestly improved prognosis., (© 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: The current study was performed to identify factors that are present at the time of breast cancer (BC) diagnosis that are associated with a higher rate of central nervous system metastasis (CNSm)., Methods: The authors analyzed a database of patients with a confirmed diagnosis of BC who were referred for a neuro-oncology consultation at the National Cancer Institute in Mexico City, Mexico, from June 2009 to June 2017. Information was collected prospectively and included demographic, pathologic, and clinical data at the time of diagnosis of BC. Bivariate and multivariate logistic regression models were built to estimate the associations between the development of CNSm and the time after BC diagnosis., Results: Among 970 patients with BC, 263 (27%) were diagnosed with CNSm. The median time from BC diagnosis to the development of CNSm was 33 months (interquartile range, 15-76 months). After multivariate analysis, age <50 years at the time of BC diagnosis (odds ratio [OR], 2.5; 95% confidence interval [95% CI], 1.8-3.5 [P < .0001]), human epidermal growth factor receptor 2 (HER2)-positive status (HER2+) (OR, 3.6; 95% CI, 2.1-6.1 [P < .0001]), luminal B/HER2+ subtype (OR, 3.1; 95% CI, 1.9-5.3 [P < .001]), triple-negative subtype(OR, 2.4; 95% CI, 1.5-4 [P = .001]), and Karnofsky performance status ≤70 (OR, 6.6; 95% CI, 4.5-9.6 [P < .0001]) were associated with a higher frequency of CNSm. Brain parenchyma was the most common site of CNSm. The median overall survival after a diagnosis of CNSm was 12.2 months (95% CI, 9.3-15.1 months)., Conclusions: CNSm is not uncommon among patients with BC, particularly in those with neurologic symptoms who require neuro-oncology evaluation and are aged <50 years at the time of diagnosis, have HER2+ or triple-negative subtypes, have a poor Karnofsky performance status, and/or have ≥2 non-CNS metastases., (© 2020 American Cancer Society.)

Optimal treatment outcomes for breast cancer are dependent on a timely diagnosis followed by an organized, multidisciplinary approach to care. However, in many low- and middle-income countries, effective care management pathways can be difficult to follow because of financial constraints, a lack of resources, an insufficiently trained workforce, and/or poor infrastructure. On the basis of prior work by the Breast Health Global Initiative, this article proposes a phased implementation strategy for developing sustainable approaches to enhancing patient care in limited-resource settings by creating roadmaps that are individualized and adapted to the baseline environment. This strategy proposes that, after a situational analysis, implementation phases begin with bolstering palliative care capacity, especially in settings where a late-stage diagnosis is common. This is followed by strengthening the patient pathway, with consideration given to a dynamic balance between centralization of services into centers of excellence to achieve better quality and decentralization of services to increase patient access. The use of resource checklists ensures that comprehensive therapy or palliative care can be delivered safely and effectively. Episodic or continuous monitoring with established process and quality metrics facilitates ongoing assessment, which should drive continual process improvements. A series of case studies provides a snapshot of country experiences with enhancing patient care, including the implementation of national cancer control plans in Kenya, palliative care in Romania, the introduction of a 1-stop clinic for diagnosis in Brazil, the surgical management of breast cancer in India, and the establishment of a women's cancer center in Ghana., (© 2020 American Cancer Society.)

Background: Frequent recurrent mutations in the breast and ovarian cancer susceptibility (BRCA) genes BRCA1 and BRCA2 among Hispanics, including a large rearrangement Mexican founder mutation (BRCA1 exon 9-12 deletion [ex9-12del]), suggest that an ancestry-informed BRCA-testing strategy could reduce disparities and promote cancer prevention by enabling economic screening for hereditary breast and ovarian cancer in Mexico., Methods: In a multistage approach, 188 patients with cancer who were unselected for family cancer history (92 with ovarian cancer and 96 with breast cancer) were screened for BRCA mutations using a Hispanic mutation panel (HISPANEL) of 115 recurrent mutations in a multiplex assay (114 were screened on a mass spectroscopy platform, and a polymerase chain reaction assay was used to screen for the BRCA1 ex9-12del mutation). This was followed by sequencing of all BRCA exons and adjacent intronic regions and a BRCA1 multiplex ligation-dependent probe amplification assay (MLPA) for HISPANEL-negative patients. BRCA mutation prevalence was calculated and correlated with histology and tumor receptor status, and HISPANEL sensitivity was estimated., Results: BRCA mutations were detected in 26 of 92 patients (28%) with ovarian cancer, in 14 of 96 patients (15%) with breast cancer overall, and in 9 of 33 patients (27%) who had tumors that were negative for estrogen receptor, progesterone receptor, and human epithelial growth factor 2 (triple-negative breast cancer). Most patients with breast cancer were diagnosed with locally advanced disease. The Mexican founder mutation (BRCA1 ex9-12del) accounted for 35% of BRCA-associated ovarian cancers and 29% of BRCA-associated breast cancers. At 2% of the sequencing and MLPA cost, HISPANEL detected 68% of all BRCA mutations., Conclusions: In this study, a remarkably high prevalence of BRCA mutations was observed among patients with ovarian cancer and breast cancer who were not selected for family history, and the BRCA1 ex9-12del mutation explained 33% of the total. The remarkable frequency of BRCA1 ex9-12del in Mexico City supports a nearby origin of this Mexican founder mutation and may constitute a regional public health problem. The HISPANEL mutation panel presents a translational opportunity for cost-effective genetic testing to enable breast and ovarian cancer prevention., (© 2014 American Cancer Society.)

Background: Triple-negative breast cancer (TNBC) is defined as breast cancer that is negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. TNBC represents 15% of all invasive breast cancers, but some studies have suggested that its prevalence differs between races. To the authors' knowledge, no previous studies have determined the prevalence of TNBC and its risk factors among Hispanic women., Methods: The authors identified 2074 Hispanic women with breast cancer who attended the National Cancer Institute in Mexico City from 1998 to 2008. All histopathologic and immunohistochemical diagnoses were rereviewed by a breast cancer pathologist. The prevalence of TNBC, its association with clinicopathologic characteristics, and its prognostic impact were determined., Results: The median patient age at diagnosis (±standard deviation) was 50 ± 12 years. The overall prevalence of TNBC was 23.1%. Younger age (P < .001), premenopausal status (P = .002), increased parity (P = .029), hormonal contraceptive use (P = .04) high histologic grade (P < .001), and advanced disease (P < .001) were associated independently with TNBC. Postmenopausal patients who had a body mass index (BMI) <25 kg/m(2) (P = .027) or <30 kg/m(2) (P < .001) were more likely to have TNBC. In multivariate analysis, patients with TNBC had a higher risk of locoregional recurrence (LRR), lower disease-free survival (DFS) (hazard ratio, 1.62; 95% confidence interval, 1.13-2.32; P = .009), and a lower cancer-specific survival (CSS) rate (hazard ratio, 1.66; 95% confidence interval, 1.20-2.30; P = .002) than patients with non-TNBC., Conclusions: The median age at diagnosis of Hispanic women with breast cancer was 11 years younger than the average age reported in the United States. The prevalence of TNBC in this study population was higher than that reported in white women with breast cancer. TNBC was associated with a higher risk of LRR and with lower DFS and CSS than those in patients with non-TNBC., (Copyright © 2011 American Cancer Society.)