Background

Incidence rates for breast cancer are higher among Mexican-American (MA) women in the United States than women living in Mexico. Studies have shown higher prevalence of breast cancer risk factors in more acculturated than less acculturated Hispanic/Latinas in the United States. We compared the prevalence of behavioral risk factors and family history of breast cancer by level of acculturation and country of residence in women of Mexican descent.

Methods

Data were collected from 1,201 newly diagnosed breast cancer patients living in Mexico (n = 581) and MAs in the United States (n = 620). MA participants were categorized into three acculturation groups (Spanish dominant, bilingual, and English dominant); women living in Mexico were used as the referent group. The prevalence of behavioral risk factors and family history of breast cancer were assessed according to acculturation level, adjusting for age at diagnosis and education.

Results

In the adjusted models, bilingual and English-dominant MAs were significantly more likely to have a body mass index of 30 kg/m(2) or greater, consume more than one alcoholic beverage a week, and report having a family history of breast cancer than women living in Mexico. All three U.S. acculturation groups were significantly more likely to have lower total energy expenditure (≤533 kcal/d) than women in Mexico. English-dominant women were significantly less likely to ever smoke cigarettes than the Mexican group.

Conclusions

Our findings add to the limited scientific literature on the relationships among acculturation, health behavior, and family history of breast cancer in Mexican and MA women.

Familial breast and ovarian cancer prevalence was assessed among 1150 women of Mexican descent enrolled in a case-only, binational breast cancer study. Logistic regression was conducted to compare odds of triple negative breast cancer (TNBC) to non-TNBC according to family history of breast and breast or ovarian cancer among 914 of these women. Prevalence of breast cancer family history in a first- and first- or second-degree relative was 13.1% and 24.1%, respectively; that for breast or ovarian cancer in a first-degree relative was 14.9%. After adjustment for age and country of residence, women with a first-degree relative with breast cancer were more likely to be diagnosed with TNBC than non-TNBC (OR=1.98; 95% CI, 1.26-3.11). The odds of TNBC compared to non-TNBC were 1.93 (95% CI, 1.26-2.97) for women with a first-degree relative with breast or ovarian cancer. There were non-significant stronger associations between family history and TNBC among women diagnosed at age <50 compared to ≥50 years for breast cancer in a first-degree relative (P-interaction = 0.14) and a first- or second-degree relative (P-interaction = 0.07). Findings suggest that familial breast cancers are associated with triple negative subtype, possibly related to BRCA mutations in Hispanic/Latina women, which are strongly associated with TNBC. Family history is an important tool to identify Hispanic/Latina women who may be at increased risk of TNBC, and could benefit from prevention and early detection strategies.

Background

We compared the distribution of breast cancer reproductive and hormonal risk factors by level of acculturation and country of residence in women of Mexican descent.

Methods

To compare the distribution of breast cancer reproductive and hormonal risk factors by level of acculturation and country of residence in women of Mexican descent, taking into account level of education, we analyzed data on 581 Mexican and 620 Mexican American (MA) women with a history of invasive breast cancer from the Ella Binational Breast Cancer Study. An eight-item language-based acculturation measure was used to classify MA women. Multivariate logistic regression was used to test associations between language acculturation, country of residence, and reproductive and hormonal risk factors.

Results

After adjustment for age and education, compared to women residing in Mexico, English-dominant MAs were significantly more likely to have an earlier age at menarche (<12 years; odds ratio [OR]=2.08; 95% confidence interval [CI], 1.30-3.34), less likely to have a late age at first birth (≥30 years; OR=0.49; 95% CI, 0.25-0.97), and less likely to ever breastfeed (OR=0.13; 95% CI, 0.08-0.21).

Conclusions

Differences in reproductive and hormonal risk profile according to language acculturation and country of residence are evident; some of these were explained by education. Results support continued efforts to educate Mexican and MA women on screening and early detection of breast cancer along with promotion of modifiable factors, such as breastfeeding.

Background

Published data support the presence of etiologic heterogeneity by breast tumor subtype, but few studies have assessed this in Hispanic populations.

Methods

We assessed tumor subtype prevalence and associations between reproductive factors and tumor subtypes in 1,041 women of Mexican descent enrolled in a case-only, binational breast cancer study. Multinomial logistic regression comparing HER2(+) tumors and triple-negative breast cancer (TNBC) to luminal A tumors was conducted.

Results

Compared with women with luminal A tumors, those with a later age at first pregnancy were less likely to have TNBC [OR, 0.61; 95% confidence interval (CI), 0.39-0.95], whereas those with three or more full-term pregnancies were more likely to have TNBC (OR, 1.68; 95% CI, 1.10-2.55). A lower odds of TNBC was shown for longer menstruation duration, whether before first pregnancy (OR, 0.78; 95% CI, 0.65-0.93 per 10 years) or menopause (OR, 0.79; 95% CI, 0.69-0.91 per 10 years). Patients who reported breastfeeding for more than 12 months were over twice as likely to have TNBC than luminal A tumors (OR, 2.14; 95% CI, 1.24-3.68). Associations comparing HER2(+) with luminal A tumors were weak or nonexistent except for the interval between last full-term pregnancy and breast cancer diagnosis.

Conclusions

Findings show etiologic heterogeneity by tumor subtype in a population of Hispanic women with unique reproductive profiles.

Impact

Identification of etiologically distinct breast tumor subtypes can further improve our understanding of the disease and help provide personalized prevention and treatment regimens.

The risk of breast cancer transiently increases immediately following pregnancy; peaking between 3-7 years. The biology that underlies this risk window and the effect on the natural history of the disease is unknown. MicroRNAs (miRNAs) are small non-coding RNAs that have been shown to be dysregulated in breast cancer. We conducted miRNA profiling of 56 tumors from a case series of multiparous Hispanic women and assessed the pattern of expression by time since last full-term pregnancy. A data-driven splitting analysis on the pattern of 355 miRNAs separated the case series into two groups: a) an early group representing women diagnosed with breast cancer ≤ 5.2 years postpartum (n = 12), and b) a late group representing women diagnosed with breast cancer ≥ 5.3 years postpartum (n = 44). We identified 15 miRNAs with significant differential expression between the early and late postpartum groups; 60% of these miRNAs are encoded on the X chromosome. Ten miRNAs had a two-fold or higher difference in expression with miR-138, miR-660, miR-31, miR-135b, miR-17, miR-454, and miR-934 overexpressed in the early versus the late group; while miR-892a, miR-199a-5p, and miR-542-5p were underexpressed in the early versus the late postpartum group. The DNA methylation of three out of five tested miRNAs (miR-31, miR-135b, and miR-138) was lower in the early versus late postpartum group, and negatively correlated with miRNA expression. Here we show that miRNAs are differentially expressed and differentially methylated between tumors of the early versus late postpartum, suggesting that potential differences in epigenetic dysfunction may be operative in postpartum breast cancers.

Abstract Background Natural killer (NK) cells are an important resource of the innate immune system directly involved in the spontaneous recognition and lysis of virus-infected and tumor cells. An exquisite balance of inhibitory and activating receptors tightly controls the NK cell activity. At present, one of the best-characterized activating receptors is NKG2D, which promotes the NK-mediated lysis of target cells by binding to a family of cell surface ligands encoded by the MHC class I chain-related (MIC) genes, among others. The goal of this study was to describe the expression pattern of MICA and MICB at the molecular and cellular levels in human cervical cancer cell lines infected or not with human papillomavirus, as well as in a non-tumorigenic keratinocyte cell line. Results Here we show that MICA and MICB exhibit differential expression patterns among HPV-infected (SiHa and HeLa) and non-infected cell lines (C33-A, a tumor cell line, and HaCaT, an immortalized keratinocyte cell line). Cell surface expression of MICA was higher than cell surface expression of MICB in the HPV-positive cell lines; in contrast, HPV-negative cells expressed lower levels of MICA. Interestingly, the MICA levels observed in C33-A cells were overcome by significantly higher MICB expression. Also, all cell lines released higher amounts of soluble MICB than of soluble MICA into the cell culture supernatant, although this was most pronounced in C33-A cells. Additionally, Real-Time PCR analysis demonstrated that MICA was strongly upregulated after genotoxic stress. Conclusions This study provides evidence that even when MICA and MICB share a high degree of homology at both genomic and protein levels, differential regulation of their expression and cell surface appearance might be occurring in cervical cancer-derived cells.

Purposes

Most molecular-based published studies on breast cancer do not adequately represent the unique and diverse genetic admixture of the Latin American population. Searching for similarities and differences in molecular pathways associated with these tumors and evaluating its impact on prognosis may help to select better therapeutic approaches.

Patients and methods

We collected clinical, pathological, and transcriptomic data of a multi-country Latin American cohort of 1,071 stage II-III breast cancer patients of the Molecular Profile of Breast Cancer Study (MPBCS) cohort. The 5-year prognostic ability of intrinsic (transcriptomic-based) PAM50 and immunohistochemical classifications, both at the cancer-specific (OSC) and disease-free survival (DFS) stages, was compared. Pathway analyses (GSEA, GSVA and MetaCore) were performed to explore differences among intrinsic subtypes.

Results

PAM50 classification of the MPBCS cohort defined 42·6% of tumors as LumA, 21·3% as LumB, 13·3% as HER2E and 16·6% as Basal. Both OSC and DFS for LumA tumors were significantly better than for other subtypes, while Basal tumors had the worst prognosis. While the prognostic power of traditional subtypes calculated with hormone receptors (HR), HER2 and Ki67 determinations showed an acceptable performance, PAM50-derived risk of recurrence best discriminated low, intermediate and high-risk groups. Transcriptomic pathway analysis showed high proliferation (i.e. cell cycle control and DNA damage repair) associated with LumB, HER2E and Basal tumors, and a strong dependency on the estrogen pathway for LumA. Terms related to both innate and adaptive immune responses were seen predominantly upregulated in Basal tumors, and, to a lesser extent, in HER2E, with respect to LumA and B tumors.

Conclusions

This is the first study that assesses molecular features at the transcriptomic level in a multicountry Latin American breast cancer patient cohort. Hormone-related and proliferation pathways that predominate in PAM50 and other breast cancer molecular classifications are also the main tumor-driving mechanisms in this cohort and have prognostic power. The immune-related features seen in the most aggressive subtypes may pave the way for therapeutic approaches not yet disseminated in Latin America.

Clinical trial registration

ClinicalTrials.gov (Identifier: NCT02326857).