A cumulative index of exposure to endogenous estrogens and breast cancer by molecular subtypes in northern Mexican women.

PURPOSE: To evaluate breast cancer (BC) molecular subtypes association with reproductive characteristics and an index of cumulative exposure to endogenous estrogens (EEI) in Mexican women. METHODS: We performed a study of incident cases and population controls in northern Mexico. We included BC cases with tumor molecular classification in their medical records (n = 509), and classified them as HR+/HER2- (ER+ and/or PR+ and HER2-) (n = 289), HER2+ (HR+ or HR-) (n = 117) or triple negative (TN) (n = 103). We matched controls (n = 1030) by age and place of residence with index cases. Women were interviewed about their reproductive history, from which the EEI was developed. We used logistic regression models to estimate BC molecular subtypes associations with reproductive characteristics and EEI. RESULTS: The EEI was higher in all subtypes compared to controls (Median HR+/HER2- 27.25, HER2+ 26.8, TN 24.2 vs. controls 22.8 years, p < 0.05), and was associated with HR+/HER2- (ORT3 vs. T1 = 2.58, 95% CI 1.77-3.55, p-trend < 0.001) and HER2+ (ORT3 vs. T1 = 4.17, 95% CI 2.15-8.08, p-trend < 0.001) BC. Additionally, HR+/HER2- tumors were positively associated with age at first pregnancy and age at menopause, and negatively with age at menarche, parity and breastfeeding. The HER2+ subtype was associated in the same direction as HR+/HER2- tumors with all the reproductive characteristics except for age at menarche. TN tumors were negatively associated with parity and breastfeeding. CONCLUSION: Endogenous estrogens exposure throughout Mexican women reproductive life may contribute to the development of all but TN BC, however, these findings should be confirmed in other Hispanic populations.

Characteristics and prognosis of stage I-III breast cancer subtypes in Brazil: The AMAZONA retrospective cohort study.

OBJECTIVE: To describe stage I-III breast cancer (BC) molecular subtypes and outcomes among a cohort of patients from Brazil. METHODS: AMAZONA study is a retrospective cohort conducted from June 2008 to January 2009 including women of at least 18 years old, with histologically proven breast cancer, diagnosed in 2001 (n = 2198) and 2006 (n = 2714). In this analysis, we included patients who underwent surgery, had stage I-III disease and available pathological information (n = 2296). We estimated molecular subtypes by local immunohistochemical stains. Data was obtained from medical charts and public databases. RESULTS: Mean age at diagnosis was 54 years and 41.1% were younger than 50 years. 23.3% were diagnosed in stage I, 53.5% in stage II and 23.2% in stage III. 80.8% were treated in the public health system. 71.3% had hormonal receptor positive disease, 15.7% were HER-2 positive and 21.1% had triple-negative breast cancer. 55.6% were treated with mastectomy and 96.2% received adjuvant treatment (82.2% chemotherapy). 13.4% of HER-2 positive patients received adjuvant trastuzumab. Overall survival rate at 5 years was 96.84% for stage I, 94.16% for stage II and 70.48% for stage III. Molecular subtypes were independent prognostic factor in stages II and III patients. CONCLUSIONS: Brazilian women have a higher risk of being diagnosed with late stage breast cancer and younger age than in high-income countries. Luminal-like disease is the most common molecular subtype in the country. Triple negative and HER-2 positive had the worst prognosis.

Expression of long non-coding RNA ENSG00000226738 (LncKLHDC7B) is enriched in the immunomodulatory triple-negative breast cancer subtype and its alteration promotes cell migration, invasion, and resistance to cell death.

Triple negative breast cancer (TNBC) represents an aggressive phenotype with poor prognosis compared with ER, PR, and HER2-positive tumors. TNBC is a heterogeneous disease, and gene expression analysis has identified seven molecular subtypes. Accumulating evidence demonstrates that long non-coding RNA (lncRNA) are involved in regulation of gene expression and cancer biology, contributing to essential cancer cell functions. In this study, we analyzed the expression profile of lncRNA in TNBC subtypes from 156 TNBC samples, and then characterized the functional role of LncKLHDC7B (ENSG00000226738). A total of 710 lncRNA were found to be differentially expressed between TNBC subtypes, and a subset of these altered lncRNA were independently validated. We discovered that LncKLHDC7B (ENSG00000226738) acts as a transcriptional modulator of its neighboring coding gene KLHDC7B in the immunomodulatory subtype. Furthermore, LncKLHDC7B knockdown enhanced migration and invasion, and promoted resistance to cellular death. Our findings confirmed the contribution of LncKLHDC7B to induction of apoptosis and inhibition of cell migration and invasion, suggesting that TNBC tumors with enrichment of LncKLHDC7B may exhibit distinct regulatory activity, or that this may be a generalized process in breast cancer. Additionally, in silico analysis confirmed for the first time that the low expression of KLHDC7B and LncKLHDC7B is associated with poor prognosis in patients with breast cancer.

Breast cancer subtype and survival among Indigenous American women in Peru.

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.

Correlation between p53 and epidermal growth factor receptor expression in breast cancer classification.

This study aimed to explore new opportunities for developing targeted therapy for triple-negative breast cancer (TNBC) by analyzing the significance and association between p53 and epidermal growth factor receptor (EGFR) expression in different molecular subtypes of breast cancer. The clinical and pathological data of 264 patients with breast cancer receiving surgery in our hospital from January 2012 to August 2013 were retrospectively analyzed. According to the expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2), Ki-67, CK5/6, p53, and EGFR detected by immunohistochemical methods, breast cancer was divided into four molecular subtypes. Then, the expression of p53 and EGFR as well as their correlation in the different subtypes were determined. Among the four subtypes, luminal B breast cancer was the most common type. TNBC and HER2-enriched breast cancer had larger tumor sizes with higher expression of Ki-67 as compared with the luminal types. TNBC had a lower lymph node metastasis rate but higher CK5/6 and EGFR expression than the other three types. The expression of p53 was higher in luminal B, HER2-enriched, and triple-negative breast cancers, and this was positively correlated with the expression of EGFR in TNBC but not in the other subtypes. p53 and EGFR expression was positively correlated in TNBC, which enables us to explore the molecular biological characteristics of TNBC, so as to provide new ideas for the treatment of TNBC.