Premenopausal African American Women Research Articles

Reproductive characteristics, menopausal status, race and ethnicity, and risk of breast cancer subtypes defined by ER, PR and HER2 status: the Breast Cancer Etiology in Minorities study

BackgroundAssociations between reproductive factors and risk of breast cancer differ by subtype defined by joint estrogen receptor (ER), progesterone receptor (PR), and HER2 expression status. Racial and ethnic differences in the incidence of breast cancer subtypes suggest etiologic heterogeneity, yet data are limited because most studies have included non-Hispanic White women only.MethodsWe analyzed harmonized data for 2,794 breast cancer cases and 4,579 controls, of whom 90% self-identified as African American, Asian American or Hispanic. Questionnaire data were pooled from three population-based studies conducted in California and data on tumor characteristics were obtained from the California Cancer Registry. The study sample included 1,530 luminal A (ER-positive and/or PR-positive, HER2-negative), 442 luminal B (ER-positive and/or PR-positive, HER2-positive), 578 triple-negative (TN; ER-negative, PR-negative, HER2-negative), and 244 HER2-enriched (ER-negative, PR-negative, HER2-positive) cases. We used multivariable unconditional logistic regression models to estimate subtype-specific ORs and 95% confidence intervals associated with parity, breast-feeding, and other reproductive characteristics by menopausal status and race and ethnicity.ResultsSubtype-specific associations with reproductive factors revealed some notable differences by menopausal status and race and ethnicity. Specifically, higher parity without breast-feeding was associated with higher risk of luminal A and TN subtypes among premenopausal African American women. In contrast, among Asian American and Hispanic women, regardless of menopausal status, higher parity with a breast-feeding history was associated with lower risk of luminal A subtype. Among premenopausal women only, luminal A subtype was associated with older age at first full-term pregnancy (FTP), longer interval between menarche and first FTP, and shorter interval since last FTP, with similar OR estimates across the three racial and ethnic groups.ConclusionsSubtype-specific associations with reproductive factors overall and by menopausal status, and race and ethnicity, showed some differences, underscoring that understanding etiologic heterogeneity in racially and ethnically diverse study samples is essential. Breast-feeding is likely the only reproductive factor that is potentially modifiable. Targeted efforts to promote and facilitate breast-feeding could help mitigate the adverse effects of higher parity among premenopausal African American women.

Abstract PO4-21-01: Recurrent Desmoid Tumor and Ductal Carcinoma In Situ in an African-American Woman: A Case Report and Discussion on Disparities for These Two Cancer Subtypes

Abstract Introduction: Disparities in cancer care in patients from different races and ethnicities unfortunately do exist and are well described in literature. Hormonal-driven cancers, such as some soft-tissue tumors and DCIS, have been demonstrated to impact African-American women (AAW) disproportionately. These patients are at increased risk for not only development of these cancers, but also experience disparities in survival, treatment outcomes, and modalities of treatment. Clinical Case: A 47-year-old premenopausal AAW with past medical history of recurrent desmoid sarcoma of the abdomen and ductal carcinoma in-situ (DCIS) of the left breast presented to oncology clinic with recurrent abdominal mass. The patient was originally diagnosed with DCIS in the left breast in 2018 and subsequently underwent left breast mastectomy with TRAM reconstruction and fat graft later that year. In 2020, the patient noticed a left lower abdominal growth that quickly enlarged and became painful. She underwent imaging without biopsy and was taken to surgery in April 2021 with tumor removal and mesh placement. Pathology showed desmoid fibromatosis infiltrating skeletal muscle and involving the inked resection margin of the specimen. Conservative re-excision and additional therapy was recommended but not done at the time. In 2022, the patient had resection of the area again with pathology of the incisional scar showing skin and deep soft tissue foci suspicious for recurrent desmoid fibromatosis extending to the inked deep margin. No mesh was placed, and the wound closed almost completely. The patient was not aware of positive margins at the time. In January 2023, patient again notice a new bump that was bothersome. Initial CT and MRI without finding of defined mass, but with right rectus thickening and enlarged right external iliac lymph node. Core biopsy in June 2023 confirmed recurrent desmoid fibromatosis. In April 2023, annual screening with mammogram was performed with a finding of 2.9 cm cluster of heterogenous calcification in the right breast. Diagnostic mammogram and ultrasound performed. Core needle biopsy was subsequently performed in May with pathology consistent with high grade DCIS with low ER and PR positivity. Lymph node biopsy was negative, but clinically positive. She is currently undergoing further genetic testing with surgical workup for mastectomy. Discussion and Conclusion: AAW diagnosed with DCIS have higher all-cause and disease specific mortality in comparison to white women (WW) diagnosed with DCIS. AAW are also at increased risk of aggressive secondary breast cancers in both the ipsilateral and contralateral breast in comparison to other races. In regards to tumor biology, WW have been shown to have higher ER and PR positivity in both primary and primary breast cancers than AAW. In many of these large-scale studies higher mortality, recurrence, and metastasis in AAW have been identified regardless of treatment modality. Research into differences in treatment between AAW and WW has shown that AAW, in contrast to our patient case, are more likely to undergo endocrine and radiation therapy rather than mastectomy. Although there does not seem to be an increased risk of desmoid fibromatosis in AAW when compared to WW, other soft-tissue tumors and malignancies do show a predilection for AAW. Incidence of sarcoma in black patients is higher than white patients, and black patients also have poorer survival outcomes. This case provides an example of the intersectionality of two cancer subtypes that impact black patients disproportionately. More evidence is required to unearth the reasons why these two cancer subtypes which are driven by similar processes impact AAW to a greater degree. Citation Format: Vinita Akula, Jessica Jones. Recurrent Desmoid Tumor and Ductal Carcinoma In Situ in an African-American Woman: A Case Report and Discussion on Disparities for These Two Cancer Subtypes [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-21-01.

Abstract PO5-09-08: Cancer Health Disparities among non-Hispanic African women: A systematic review of the disparities, reasons and probable intervention

Abstract Health equity places health inequities in historical and social context and calls for action to address injustice and enhance health. As an ethical and human rights value that drives us to end health inequities, health equality is defined as everyone having a fair and just opportunity to be as healthy as feasible. According to this perspective, structural discrimination and marginalization cause health disparities that can be avoided. If these issues are not resolved, social and economic injustices, bias, and unfavorable outcomes that affect all of us will continue to exist. The idea of cancer health equality recognizes that there is still considerable work to be done to change the social structures and historical momentum that have contributed to different cancer outcomes, and that this work can only succeed if it is done. In USA, non-Hispanic black women experience a complicated and multifaceted disparity in breast cancer incidence and outcome. It's possible that social, economic, and behavioral variables contribute to discrepancies. Black women are less likely to breastfeed after childbirth, statistically more likely to have diabetes, heart disease, and obesity, all of which are risk factors for breast cancer. Compared to white women, they are more likely to lack adequate health insurance or access to medical facilities, which could have an impact on screening, follow-up treatment, and therapy completion. It has become evident via more study that biology also plays a part. Black women are more likely to be diagnosed at younger ages and at higher rates with more aggressive subtypes of breast cancer, such as triple-negative breast cancer (TNBC) and inflammatory breast cancer. The National Institute on Minority Health and Health Disparities (NIMHD) established a research framework to characterize the multiple domains of influence (biological, behavioral, physical environment, sociocultural environment, and health care system) that may act across various levels of influence to impact health. A literature search was conducted using the National Library of Medicine's PubMed search engine. Triple negative breast cancer (TNBC) is a common malignancy in African American women. The incidence of TNBC is higher in women of African ancestry and is associated with overall poor prognosis. This disparity is due to the presence/absence of oncogenes/tumor suppressor genes, mutations and altered signaling pathways that might predispose premenopausal African American women to TNBC. Multiple socioeconomic factors influence the access to standard care, novel treatments and inclusion in clinical trials and contribute to overall prognoses. This review focuses on the epidemiology, molecular alterations, and treatment-related disparities in African Americans with breast cancer. This poster will elaborate the racial disparity in terms of breast cancer among the African-American women in USA, the reasons and it's effects on health equity. Citation Format: Tasnuva Khan Efa. Cancer Health Disparities among non-Hispanic African women: A systematic review of the disparities, reasons and probable intervention [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-09-08.

Acute insulin response following exercise and its association to lipid changes in sedentary African-American women

Sedentary African-American (AA) women are at increased risk of hypertension, dyslipidemias, metabolic syndrome, and impaired insulin response to exercise. The purpose of the study was to determine the effects of a single bout of aerobic exercise on fasting serum insulin and glucose concentrations following 1464 kJ (350 kcal) of exercise and to determine if this response was associated with serum lipid concentrations in overweight AA women. Premenopausal AA women (n = 11, mean ± SD, age = 32.5 ± 4.8 yr., BMI = 29.8 ± 4.8 kg·m-2, % fat = 35.6 ± 6.3, VO2peak = 21.5 ± 3.6 ml·kg-1·min-1, total cholesterol = 4.8 ± 0.6 mmol·L-1, triglycerides = 0.60 ± 0.2 mmol·L-1, HDLC = 3.3 ± 0.5 mg·dL-1) performed 1464 kJ (350 kcal) of treadmill exercise at 60%-70%VO2peak. Fasting plasma insulin and glucose concentrations were collected 24-h prior to, and immediately, 24-h, and 48 h following exercise. Fasting insulin concentration increased immediately following exercise (Baseline=77.1 ± 10.42 vs. Immediately=117.4 ± 15.28 μU·mL-1, 95%CI= 32.71, 47.89; P<0.05). The change in insulin concentration from 24-h pre- to 24-h post-exercise was correlated with BMI (r= 0.51), VO2peak (r= -0.47), and the change in lipoprotein lipase activity (r=0.37) (P<0.05 for all). In conclusion, in sedentary AA women, the insulin response immediately following exercise may be elevated, and is not suppressed below pre-exercise concentrations during the 48-h following exercise. The insulin response 24-h following exercise is modestly associated with markers of lipoprotein metabolism.

GRANULAR CELL TUMOR OF THE BREAST - A DIAGNOSIS TO CONSIDER: CASE REPORT AND LITERATURE REVIEW

Granular Cell Tumors (GCTs) or Abrikossoffs tumors are ubiquitous lesions that are currently assumed to arise from perineural Schwan cells. Granular Cell Tumors of the Breast (GCTBs) are rare tumors, representing about 5 to 15 % of all GCTs and 6,7 out of 1000 cases of breast neoplasms. They occur usually in premenopausal African-American women and are by large benign, even though in extremely rare cases they can express malignant behavior or coexist with malignant lesions. GCTBs are of particular significance as they mimic breast malignancies both clinically and radiologically. Histological examination is mandatory for the diagnosis of GCTBs and IHC seems to be the gold standard for this diagnosis, indeed, our tumor cells show strong positivity for the S-100 protein. Wide local excision is the only treatment for GCTBs that are associated with an excellent prognosis. In this article we report a case of GCTB with a brief literature review, the aim of this work is to draw the attention of senologists and pathologists toward this misleading tumor, wich should be routinely recalled as differential diagnosis of breast malignancies in order to avoid over treatement of patients.

Abstract PO-148: The role of annexin A6 in triple-negative breast cancer metabolism and disease progression

Abstract Triple-negative breast cancer (TNBC), which accounts for up to 17% of all breast cancer cases in the Unites States, disproportionately affects premenopausal African American and Hispanic women. Here, we report the synergistic function of the tumor suppressor annexin-A6 (AnxA6) and Lapatinib-resistance (Lap-R) in the context of cellular bioenergetics. Metabolic profiling of TNBC cell lines show extensive diversity amongst basal-like (BSL) vs mesenchymal-like (MSL) molecular subtypes. Down regulation of AnxA6 in AnxA6- expressing and Lap-R cell lines attenuated mitochondrial respiration, glycolytic function, and cellular ATP production capacity, decreasing the overall metabolic plasticity of the cell. Additionally, AnxA6-depletion altered lipid metabolism by enhancing the mitochondrial uptake of cytosolic fatty acids for β-oxidation. NMR-based metabolomics revealed that AnxA6 depleted and/or Lap-R TNBC cells have a greater dependency on gluconeogenic precursors including glycine, alanine, lactic acid, and oxaloacetic acid as survival mechanisms. Taken together, this study proposes that altered expression of AnxA6 is accompanied by significant bioenergetic adaptations and hence provide novel insights into the failure of EGFR-targeted therapies as therapeutic options and disease progression in patients with triple-negative breast cancer. Citation Format: Stephen D. Williams, Sarrah E. Widatalla, Amos M. Sakwe. The role of annexin A6 in triple-negative breast cancer metabolism and disease progression [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-148.

Cumulative menstrual months and breast cancer risk by hormone receptor status and ethnicity: The Breast Cancer Etiology in Minorities Study.

Reproductive and hormonal factors may influence breast cancer risk via endogenous estrogen exposure. Cumulative menstrual months (CMM) can be used as a surrogate measure of this exposure. Using harmonized data from four population-based breast cancer studies (7284 cases and 7242 controls), we examined ethnicity-specific associations between CMM and breast cancer risk using logistic regression, adjusting for menopausal status and other risk factors. Higher CMM was associated with increased breast cancer risk in non-Hispanic Whites, Hispanics and Asian Americans regardless of menopausal status (all FDR adjusted P trends=.0004), but not in African Americans. In premenopausal African Americans, there was a suggestive trend of lower risk with higher CMM. Stratification by body mass index (BMI) among premenopausal African American women showed a nonsignificant positive association with CMM in nonobese (BMI <30 kg/m2 ) women and a significant inverse association in obese women (OR per 50 CMM=0.56, 95% CI 0.37-0.87, Ptrend =.03). Risk patterns were similar for hormone receptor positive (HR+; ER+ or PR+) breast cancer; a positive association was found in all premenopausal and postmenopausal ethnic groups except in African Americans. HR- (ER- and PR-) breast cancer was not associated with CMM in all groups combined, except for a suggestive positive association among premenopausal Asian Americans (OR per 50 CMM=1.33, P=.07). In summary, these results add to the accumulating evidence that established reproductive and hormonal factors impact breast cancer risk differently in African American women compared to other ethnic groups, and also differently for HR- breast cancer than HR+ breast cancer.

Abstract B071: PVT1 regulation of claudin expression in triple-negative breast cancer

Abstract Breast cancer (BC) is a heterogeneous disease that is classically driven by the estrogen receptor (ER), progesterone receptor (PR) and human epithelial growth factor receptor 2 (EGFR2/HER2) signaling pathways. Triple negative breast cancer (TNBC), is a lethal subtype of invasive BC tumors that are ER-, PR- and HER2-. A subtype of TNBC is claudin low (CL). Dysregulation of claudin proteins disrupts tight junctions, consequently inducing the epithelial-to-mesenchymal transition (EMT) in cancers. This leads to enhanced motility and metastasis. Patients with CL TNBC have worse prognosis than patients with other BC subtypes. African American (AA) women with TNBC account for almost 20% of all BC cases and premenopausal African American (AA) women are more likely to die from the disease. PVT1 is a long noncoding RNA (lncRNA) transcribed from the 8q24 genomic locus that has been implicated in multiple cancers including BC. Amplification of the 8q24 gene locus is a common event in many malignant diseases and is associated with poor survival rate among patients. Although previous research demonstrates a critical functional role which PVT1 plays in BC, the underlying molecular mechanisms of PVT1 in CL TNBC was previously unknown. We assessed PVT1 expression in BC, and we observed that PVT1 exons 4A, 4B, and 9 are significantly upregulated in MDA MB 231 cells (claudin low) and significantly downregulated in MDA MB 468 cells (claudin high), in comparison to T47D (ER+). We have confirmed that claudin expression, specifically claudins 1, 3, 4 and 7, are higher in MDA MB 468 and lower in MDA MB 231. When PVT1 exon 9 expression is silenced in the MDA MB 231 CL TNBC cell line, we observed a significant reduction in migration when compared to cells transfected with a control scramble siRNA, suggesting that PVT1 exon 9 may be regulating migration in CL TNBC. Further investigation could lead to an understanding of the molecular mechanisms by which PVT1 exon 9 regulates claudin expression and consequently clinical outcome in TNBC. Citation Format: Fayola Levine, Olorunseun Ogunwobi. PVT1 regulation of claudin expression in triple-negative breast cancer [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B071.

Abstract C47: Obesity enhances tumor colonization and promotes expression of the spliced variant MBD2_v2 and splicing factor SRSF2 in triple-negative breast cancer

Abstract Introduction: Triple-negative breast cancer (TNBC) is a molecular subtype that accounts for approximately 15-20% of invasive breast cancer diagnoses in the United States. TNBC occurs more prevalently in premenopausal African American women (AAW), and obesity coupled with chronic inflammation is a risk factor for both incidence and recurrence. TNBC is lacking therapeutic options and persons diagnosed with TNBC have the lowest 5-year survival rates among all breast cancer patients, with AAW disproportionally bearing this burden. In order to improve TNBC patient outcomes, etiologic factors driving disparities in disease progression need to be better understood. We previously showed in TNBC cell cultures that intrinsic oncogenic redox signaling promotes self-renewal capacity of cancer stem-like cells (CSC) by maintaining expression of an epigenetic reader protein and mRNA spliced variant, methyl binding domain protein 2 variant 2 (MBD2_v2). We hypothesized that obesity-induced chronic inflammation in vivo could promote a similar cancer phenotype. Methods: To study this potential phenomenon, we developed and characterized a diet-induced obesity mouse tumor xenograft (MTX) model of TNBC in C57BL/6J Rag1 (-/-) mice, a strain that maintains a functional innate immune system, to recapitulate the proinflammatory environment induced by increased adiposity. TNBC cell lines MDA-MB-468 and MDA-MB-231 were used to generate ectopic tumor xenografts in this model. Tumor colonization and growth were measured over 150 days. RT-PCR and microarray based assays were used to detect transcriptional changes in TNBC MTXs. Results: At 5 weeks post-diet consumption, mice fed a high-fat diet displayed a 5-10% increase in body weight and increased blood glucose concentration. By the end of the study high-fat fed mice displayed a 33-43% increase in body weight and appeared to have greater central adiposity post-mortem. In overweight mice relative to healthy weight controls, TNBC cell line tumor colonization rate and MBD2_v2 expression were significantly higher. Furthermore, staining for CSC marker EpCam was greater in overweight versus control MTXs, indicating that CSC self-renewal capacity could have been enhanced. Upon global gene expression analysis of overweight MTXs, we observed a significant upregulation of stem-related factors based on fold-change expression, as well as functional enrichment for RNA splicing, including SRSF2, a splicing factor that has been shown to drive MBD2_v2 expression in pluripotent stem cells. Knockdown of SRSF2 led to decreased expression of MBD2_v2 in MDA-MB-468 cells, and decreased CSC self-renewal capacity in vitro. Conclusions: Altogether these data support MBD2_v2 regulation by redox signaling, which may be driven by a proinflammatory environment in the presence of increased adiposity. Future studies will be conducted to confirm MBD2_v2's importance in obesity-related tumor colonization in in vivo overexpression and knockdown studies, and to determine its transcriptional regulatory functions in TNBC. Citation Format: Emily A. Girsch, Gregory Dyson, Cristina Mitrea, Bin Bao, Lisa Polin, Aliccia Bollig-Fischer. Obesity enhances tumor colonization and promotes expression of the spliced variant MBD2_v2 and splicing factor SRSF2 in triple-negative breast cancer [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr C47.

Biopsychosocial Challenges and Needs of Young African American Women with Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is a subtype of breast cancer known to have poorer prognoses and lower survival rates compared with other types of breast cancer. In addition, TNBC is overrepresented in premenopausal African American women. Using grounded theory as the qualitative methodological approach, the present article elucidates unique biopsychosocial challenges and needs of young African American women with TNBC. A study group of six women with TNBC and a comparison group of six women with estrogen receptor-positive breast cancer were interviewed longitudinally over three time points throughout the cancer treatment trajectory. Major themes that were unique to the study group of women with TNBC include (a) longer, more aggressive treatment trajectories; (b) more difficult struggles with feminine identity; (c) the presence of fertility and parenting issues; (d) higher burdens of care; (e) barriers to separation and individuation as a maturation milestone; and (f) feeling out of place compared with peers. These themes provide a foundation to inform how social workers care for this underserved group of women.

Biology and Etiology of Young-Onset Breast Cancers among Premenopausal African American Women: Results from the AMBER Consortium.

Background: African American (AA) women have higher incidence of aggressive, young-onset (<40 years) breast cancers. Young- and older-onset disease may have distinct tumor biologies and etiologies; however, studies investigating age differences among AA women have been rare and generally underpowered.Methods: We examined tumor characteristics and breast cancer risk factors associated with premenopausal young (<40) vs. older (≥40) AA women's breast cancer in the African American Breast Cancer Epidemiology and Risk Consortium (2,008 cases and 5,144 controls). Unconditional logistic regression models assessed heterogeneity of tumor biology and risk factor associations by age, overall, and by estrogen receptor status.Results: Premenopausal AA women <40 years had higher frequency of poorer-prognosis tumor characteristics compared with older women, including negative estrogen and progesterone receptor status, triple-negative subtype, higher grade, higher stage, and larger tumors. Adiposity (i.e., waist-to-hip ratio) and family history of breast cancer were more strongly associated with young-onset disease [case-control OR = 1.46, 95% confidence interval (CI) = 1.04-2.05; OR = 3.10, 95% CI = 2.08-4.63, respectively] compared with older-onset disease (OR = 1.11, 95% CI = 0.91-1.35; OR = 1.57, 95% CI = 1.26-1.94). Breastfeeding showed a slight inverse risk association among young women (OR = 0.70, 95% CI = 0.43-1.16). Oral contraceptive use was associated with increased risk regardless of age. Considering various cutoff points for young age (<40, <45, <50), age-related heterogeneity was greatest when <40 was used.Conclusions: Among premenopausal AA women, diagnosis before age 40 is associated with more aggressive breast tumor biology and some etiologic differences.Impact: Modifiable risk factors including breastfeeding, adiposity, and oral contraceptive use may be important targets for mitigating harms of young-onset breast cancer. Cancer Epidemiol Biomarkers Prev; 26(12); 1722-9. ©2017 AACR.

Highlights of This Issue

It is increasingly recognized that black women and young women both experience higher frequency of aggressive breast tumors, but few studies have been adequately powered to evaluate risk factor associations in this group of women. In this consortium analysis of breast cancer among premenopausal African American women, distinct risk factor associations were observed for young women, with increased risk associated with higher abdominal adiposity, family history, oral contraceptive use, and lower breastfeeding. This study by Chollet-Hinton and colleagues reveals age-related differences in breast cancer biology and etiology among African American women and identifies potentially modifiable targets to reduce the burden of young-onset breast cancer.Mobile screening units have been used for the early detection of cancer for more than 60 years, yet no review has summarized the international evidence regarding their performance. Greewald and colleagues conducted a systematic review to describe mobile screening unit interventions, uncovering 78 studies located in 20 countries, offering mostly breast and cervical cancer screening. Mobile screening units represent an innovative method for offering screening services in low-infrastructure regions, including lower income countries, and may prove to be an important tool for reducing inequalities in access to early detection and treatment.Cancer survivors are living longer today and need to be aware of long-term disease risks that can result from a combination of their cancer treatment and lifestyle factors. Blackburn and colleagues conducted a cohort study of 3,700 thyroid cancer patients and 15,600 individuals from the general population. They observed that thyroid cancer patients diagnosed at young ages (&lt; 40 years old) were at increased risk of various aging-related diseases, such as diabetes, heart disease, and osteoporosis. More research that focuses on cancer survivors' long-term experiences and how we can personalize their preventive care is needed.It is not clear to what extent alcohol, smoking, and physical activity are associated with the various subtypes of breast cancer. Ellingjord-Dale and colleagues conducted a case–control study nested within a large cohort from the Norwegian Breast Cancer Screening Program during 2006 to 2014. Alcohol consumption was associated with an increased risk of luminal A–like breast cancer, while physical activity was associated with a decreased risk. Smoking was positively associated with both luminal A–like and luminal B–like HER2 negative breast cancer. In this large study, alcohol, smoking, and physical activity were predominantly associated with the most common types of breast cancer.

Abstract 1132: Lactate dehydrogenase expression in African American women with triple-negative breast cancer

Abstract The incidence of breast cancer in African American women (AAW) is much lower than those of their Caucasian counterparts. However, the age adjusted mortality rates are much greater for AAW compared to Caucasian American women (CAW). These differences in survival between AAW and CAW were attributed to socioeconomic factors and access to health care. Yet, after adjusting these differences, AAW still had lower survival rates than CAW. Genetic and immunohistochemical studies have revealed that biological variations may account for this disparity. These studies have suggested as a causative: a higher prevalence of basal-like tumors in premenopausal AAW and low prevalence of luminal tumor. These are characterized by being high-grade aggressive tumors that are estrogen receptor negative (ER-), progesterone receptor negative (PR-), human epidermal growth factor receptor-2 (HER-2) +/-; with high rate of lymph node involvement. Despite this understanding, there is little evidence to indicate which genetic or non-genetic factors contribute to causing aggressive breast cancer thereby limiting the development of prevention and treatment option. We proposed that the phenotypic diversity of breast cancer might be accompanied by a corresponding diversity in protein expression patterns that can be reveal using proteomic technologies. We hypothesized that in addition to ER- and PR-, and the absence in expression of HER-2, the protein composition of triple-negative tumors varies among African-American and Caucasian. Two-dimensional gel electrophoresis, mass spectrophotometry and data analysis of protein from breast cancer tissues were used to identify differentially expressed proteins from African American and Caucasian women. Western blot of luminal and TNBC cell lines were used to confirm the expression of identified proteins. We have found that many proteins were differentially expressed in AAW breast cancer tissues compared to CAW. One of these is lactate dehydrogenase which was found to be overexpressed in tissues from AAW. Western blot analysis confirmed expression. Citation Format: Odalys J. Torres-Luquis, Sulma Mohammed. Lactate dehydrogenase expression in African American women with triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1132. doi:10.1158/1538-7445.AM2017-1132

The association between subjective assessment of menstrual bleeding and measures of iron deficiency anemia in premenopausal African-American women: a cross-sectional study.

BackgroundBoth iron deficiency and iron deficiency anemia are common in the United States with a prevalence amongst women of 12 % and 4 % respectively. These numbers are even higher in African-American women (AAW) and are often a result of heavy menstrual bleeding (HMB). The primary objective of this study was to determine if perceived assessment of menstrual bleeding was associated with objective and subjective measures of anemia in AAW.MethodsQuantitative cross-sectional pilot study with surveys and venipuncture.Results44 premenopausal AAW (mean age 37.9 years ± 9. 4) participated in the study. Iron deficiency was present in 68.2 % of the participants and 18.2 % were anemic. Almost half of the participants reported that their menses were heavy or very heavy, and there was a relationship between perceived heaviness of menstrual flow and anemia (P = 0.021). Of the individuals who reported that their menses were heavy or very heavy, 35.0 % were anemic. AAW who reported heavy or very heavy menses had significantly lower hemoglobin (P = 0.015), hematocrit (P = 0.003), and ferritin (P = 0.012) levels, as well as more general (P = 0.006) and menses-associated symptoms of anemia (P = 0.015) than those who reported normal or light menses.ConclusionsThis pilot study of premenopausal AAW found that a significant percentage of women who report HMB are not only iron deficient, but also anemic. AAW should be educated on the consequences of HMB and counseled to seek care with a women’s health provider when they perceive HMB. More importantly, providers should be aware that when AAW report HMB, evaluation for iron deficiency and anemia are essential.Electronic supplementary materialThe online version of this article (doi:10.1186/s12905-016-0329-z) contains supplementary material, which is available to authorized users.

Abstract 2606: Chemo-preventive efficacy of a natural product anti-cancer agent which surpasses Taxol

Abstract Breast cancer (BC), a major public health problem, is one of the leading causes of cancer-related deaths among women. In particular, triple-negative breast cancer (TNBC), the most aggressive form of BC poses significant therapeutic challenges. TNBCs are most common in women with BRCA1 gene mutations, younger women, and in pre-menopausal African American (AA) women compared to White women, significantly contributing to health disparities. Consisting of many heterogeneous, undifferentiated cell types including very high mammary cancer stem cell (MCSCs) content, TNBCs are diseases with high recurrence rates. Combining therapeutics to target a variety of growth pathways has inhibited growth and shrunk aggressive TN tumors. Yet, a major drawback of such therapy is the severe side effects commonly used chemotherapeutic agents have on normal cells. Therefore there is a critical need to develop new combinations of therapeutics that target MCSCs and improve the anticancer effects, while reducing harmful side effects. We present compelling preliminary findings comparing the anticancer effects of aqueous extracts of a plant, Vernonia amygdalina (VA), alone or in combination with Paclitaxel (TAX) in vitro and against TNBC cells injected into athymic mice intra-peritoneally. The effects of TAX alone or VA extracts alone or with TAX, were evaluated in Hsd:Athymic Nude-Foxn1nu, age 5-6 weeks, female mice inoculated subcutaneously with Hras MCSCs. Animals were grouped as follows: 1-Control, inoculated with Hras cells only; 2-VA treatment (10 mg/kg) simultaneously with injection of Hras cells, followed by 16-day VA treatment; 3-replicate of 2; 4-pretreatment with VA 10 days before injection of Hras cells, followed by 16-day VA treatment; 5-IP inoculation of TAX (10 mg/kg) simultaneously with injection of Hras cells; and 6-subcutaneous inoculation of VA (5 mg/kg) plus IP injection of TAX (5 mg/kg) simultaneously with injection of Hras cells. Studies revealed that though there was a lag in tumor growth for all treatment groups, the most significant reduction in tumor size was observed in group 4 animals, those which had been pretreated with VA each day for 10 days prior to inoculation with Hras cells. In the second round of experiments, we evaluated the efficacy of VA extracts (10-day pretreatment, high dose, 20 mg/kg) administered simultaneously with injections of both Hras cells and AA woman-derived MDA-MB-468 cells, at opposing sites, versus combined treatment with very low doses of VA and TAX (5 mg/kg of each agent, subcutaneously) toward inhibition of growth of tumors in our nude mice model. Based upon our findings, VA extract exhibits chemopreventative efficacy, addressing a major health problem which is the dominant biological cause of population-based disparities in BC mortality in the U.S. Our expectation is that this work could direct further in vivo studies and eventually translate to human clinical trials. Citation Format: Carolyn B. Howard. Chemo-preventive efficacy of a natural product anti-cancer agent which surpasses Taxol. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2606.

Abstract 4094: Exosomes secreted from the noncancerous microenvironment promote proliferation, migration, and invasion in breast cancer cells

Abstract Introduction: Triple negative breast cancer (TNBC) is one of the most aggressive forms of five major types of breast cancer. Because TNBC mortality disproportionately affects premenopausal African American women, a health disparity exists within this group. Our research has provided insight on how the noncancerous microenvironment plays a role in TNBC proliferation, migration, and invasion. Exosomes, extracellular vesicles (30-300 nm) produced ubiquitously by mammalian cells, are secreted by noncancerous breast epithelial cells, and have been noted to enhance proliferation, migration and invasion in TNBC. Therefore, the purpose of this study is to determine if exosome-free conditioned media (EFCM), which contains noncancerous MCF10A exosomes, enhances proliferation, migration and invasion in TNBC. Methods: MDA-MB-231 and MCF10A breast epithelial cells were used as cell line models. Proliferation was measured by the alamar blue proliferation assay. The transwell migration assay was used to assess migration, and the Matrigel invasion assay was used to measure migration. ExoELISA assays were also used to detect exosomes in exosome-free conditioned media (EFCM) from MCF10A cells. MCF10A cells were serum-starved for 24 hours, using DMEM/F-12 with 0.5% standard or exosome-depleted FBS (edFBS), to produce exosomal conditioned media (CM) and EFCM. This media was harvested and sterile filtered before use. MDA-MB-231 cells were treated with EFCM in each of the bioassays, and RPMI-1640 was used as a control. Results: MCF10A exosomes introduced via EFCM enhanced proliferation, migration and invasion of MDA-MB-231 cells. Conclusions: Taken together, our findings demonstrate that secreted factors from noncancerous MCF10A cells that have been stressed as a direct result of serum starvation are exosomes. These exosomes recruit TNBC cells to increase proliferation, migration, and invasion. The role of these exosomes in the noncancerous microenvironment is poorly understood, but these data suggest that exosomes from the noncancerous microenvironment have potential to be used in targeted therapies against triple negative breast disease. Citation Format: Letitia A. Yearby, Terri Cunningham, Jacenta Matthews, KiTani Parker Lemieux. Exosomes secreted from the noncancerous microenvironment promote proliferation, migration, and invasion in breast cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4094.

Current status and novel directions in triple negative breast cancer patients. Risk factors. Role of the platinum-based chemotherapy

Rationale. Breast cancer (BC) has been recognized to be the most common type of cancer in women all over the world. One of the most aggressive subtype of BC is the triple negative breast cancer (TNBC) which is defined by the absence of estrogen receptor (ER) and progesterone receptor (PR) as well as the lack of overexpression of the human epidermal growth factor 2 (HER 2). Aim. As the estrogen and progesterone receptors as well as the expression of HER2 are lacking, a targeted therapy with anti-hormone agents and anti-HER2 cannot be utilized, the therapeutic possibilities for TNBC women are limited. The aim of this review is to present the current scientific data as well as the latest research in TNBC with focus on the risk factors as well as the current role of platinum-based chemotherapeutic agents and their future implications in TNBC treatment. Method. Information about the risk factors associated to TNBC as well as the chemotherapeutic regimens was searched through Pubmed and Medline using controlled vocabulary (e.g. breast cancer) and key words (e.g. neoadjuvant, triple negative, platinum). Systematic reviews, randomized and controlled clinical trials were analyzed. No restrictions regarding date or language were used. Conclusions. TNBC is a complex and heterogeneous disease, divided into many subtypes and with an aggressive evolution. Premenopausal women and African American women are far more likely to develop TNBC. More research is required in order to confirm the association between obesity, BMI, parity, use of oral contraceptives, alcohol and cigarette smoking and TNBC. Randomized clinical trials presented at the San Antonio Symposium suggest that platinum chemotherapy play an important role in the treatment of TNBC, especially early stage TNBC. Tumor-based measures of genomic instability will help to clarify the optimal use and activity of platinum in TNBC. However, it is clear than more epidemiological studies as well as the discovery of novel therapeutic possibilities are mandatory in order to unravel the complexity of this BC subtype, hence offering a chance to women diagnosed with TNBC.

Abstract 1878: Dietary vitamin A intake and breast cancer risk among African American women: The AMBER Consortium

Abstract Introduction: Some studies in women of European descent showed an inverse association of dietary vitamin A intake with breast cancer risk, in particular, among premenopausal women. However, it is unknown whether the associations exist among women of African descent. Methods: In the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium, we included data from 2487 breast cancer cases and 11,843 controls from the three studies that had food frequency questionnaires (FFQs) (Black Women's Health Study [BWHS], Multiethnic Cohort Study [MEC], and Women's Circle of Health Study [WCHS]). Total vitamin A (preformed vitamin A from animal sources plus carotenoids from fruits and vegetable) intake in μg retinol equivalent (RE) from diet only was assessed by FFQ, and estrogen receptor (ER) status was abstracted from pathology reports. Logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI) for study-specific quintiles adjusting for age, education, body mass index, study, time period, geographical region, family history of breast cancer, age at menarche, parity, age at first birth, use of hormone replacement therapy, duration of oral contraceptive use, smoking, alcohol use, and total energy intake. Results: We observed no association of dietary total vitamin A intake with ER-positive breast cancer overall. However, dietary total vitamin A intake was inversely associated with ER-positive breast cancer among premenopausal women (quintiles 5 vs. 1: OR = 0.66, 95% CI = 0.47-0.93; p-trend = 0.022), but not among postmenopausal women (quintiles 5 vs 1: OR 1.06, 95% CI 0.81-1.39; p-trend = 0.89). There was no evidence for an association of dietary total vitamin A intake with ER-negative breast cancer, regardless of menopausal status. Only BWHS and MEC had information on multivitamin supplement use; adjusting for this variable did not change the associations in these two studies. Conclusion: A higher versus lower consumption of total vitamin A from diet was associated with a lower risk of ER-positive breast cancer among premenopausal African American women. This finding is consistent with the observation in women of European decent; the potentially beneficial influence of vitamin A on ER-positive breast cancer warrants investigation. (Funding: NIH/NCI P01 CA151135) Citation Format: Ting-Yuan D. Cheng, Susan E. McCann, Gary Zirpoli, Song Yao, Elisa V. Bandera, Laurence N. Kolonel, Lynn Rosenberg, Andrew F. Olshan, Julie R. Palmer, Christine B. Ambrosone. Dietary vitamin A intake and breast cancer risk among African American women: The AMBER Consortium. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1878. doi:10.1158/1538-7445.AM2015-1878

Abstract C16: Feasibility study: Protein profiling of primary breast cancers from premenopausal women

Abstract African American women are more likely to be diagnosed with aggressive breast cancer at a younger age, have a higher risk of death, and have a higher prevalence of obesity than their Caucasian counterparts. Moreover, African American (AA) women diagnosed with triple-negative breast cancer have the lowest survival rates of all racial/ethnic groups. Although these disparities have been attributed to differences in biology, family and reproductive history, mammographic breast density, body mass index, access to healthcare, diet and environment, more etiologic studies are needed to elucidate the complex association between race, biologic factors, and socioeconomic factors. In the present study, we tested the feasibility of using high-throughput reverse phase protein microarray to identify protein(s) that are differentially expressed in the primary invasive breast cancers of premenopausal Caucasian and African American women. We examined the expression of 60 phosphorylated, total, and cleaved proteins in microdissected epithelial cells from 26 pre-treatment primary breast cancers. The impact of obesity on protein expression was also considered by stratifying samples into non-obese and obese based on a body mass index (BMI). Samples that come from women with BMI &amp;lt; 30 kg/m2 are classified as non-obese, while those with BMI ≥ 30 kg/m2 are considered obese. All statistical analyses were done using SAS Enterprise Guide 5.1 (SAS Institute, Cary, NC). For comparison of 2 groups, t tests were used for continuous variables and Fisher exact tests for categorical variables. ANOVA was used for comparison of more than 2 groups. Two-tailed p-value &amp;lt; 0.05 was considered statistically significant. Unsupervised hierarchical clustering analysis was performed on log 2-transformed values for each protein endpoint, using average linkage of the Pearson correlation coefficient. In this exploratory study, 58% of the primary breast cancers come from Caucasian women, while 42% of the samples come from AA women. The mean age and BMI for the two groups of women did not differ significantly. While the majority of the samples were of luminal subtypes, the triple-negative breast cancers were represented in majority of AA women. The expression of MEK1/2 S217/S221, PKC pan beta S660, and total PTEN were significantly higher in Caucasian women. When the impact of breast cancer subtypes (triple-negative vs. luminal A) on protein expression was examined, only total PTEN was statistically significant. Given the role of obesity in breast cancer, we determined which proteins are differentially expressed in non-obese and obese samples. Few components of the insulin and insulin-like growth factor and inflammatory signaling pathways (e.g. PTEN, acetyl CoA carboxylase, PKC pan beta S660, Stat3) were highly expressed in samples of obese women. This preliminary data demonstrates (a) the feasibility of mapping cell signaling networks in limited number of pre-treatment samples from premenopausal women and (b) the potential of future proteomic and larger cohort studies to identify which women will likely benefit from combination of targeted agents. Citation Format: Catherine Ibarra Drendall, William Barry, Corinne Ramos, Nora Tolbert, Joseph Geradts, Emanuel Petricoin, Victoria Seewaldt. Feasibility study: Protein profiling of primary breast cancers from premenopausal women. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr C16. doi:10.1158/1538-7755.DISP13-C16

Abstract C84: Body size across the lifecourse and risk of breast cancer in African American women, the Carolina Breast Cancer Study

Abstract Background: Body size is a modifiable risk factor associated with postmenopausal breast cancer in US White women. However, in African-Americans, there have been fewer studies and relationships are not well established. Aims and Methods: We investigated the association between breast cancer risk and body size in childhood, young adulthood, and near the time of breast cancer diagnosis using data from the Carolina Breast Cancer Study, a 1993-2001 population-based case-control study of African-American (AA) cases (343 premenopausal, 445 postmenopausal) and controls frequency-matched by age and race. We investigated whether a) self-reported body size at age 10, age 18, age 35, and a year before interview and b) nurse-measured BMI, waist circumference, and waist-to-hip ratio (WHR) at interview were associated with cancer risk. Logistic regression models were adjusted for age, family history of breast cancer, education level, alcohol use, age at menarche, parity, age at first birth, and lactation. Results: For premenopausal AA women, larger body size tended to be positively associated with cancer risk. The strongest results were for WHR (0.84+ vs &amp;lt;0.77): OR=2.00 [1.28, 3.13]). For postmenopausal women, body size was not significantly associated with risk, but weak inverse associations with higher adiposity were observed for nurse-measured BMI, weight at age 10, and possibly WHR (0.84+ vs &amp;lt;0.77) (OR=1.20 [0.76, 1.89]). Conclusions: Associations between body size and breast cancer risk varied by menopausal status, measure of adiposity, and timing in the lifecourse. Strikingly, associations were not in the direction expected from the previous literature, which is based predominantly on Caucasian women. In fact, body size associations for premenopausal AA women may be inverse of that observed in Whites. Impact: African-American women have higher risk of breast cancer at young ages (&amp;lt;40 years), but the causes of this disparity are not well understood. Given that the prevalence of obesity is high among African American women, understanding how body size relates to their risk of premenopausal breast cancer may offer insights for prevention. Citation Format: Whitney Robinson, Chiu Kit Tse, Andrew F. Olshan, Melissa Troester. Body size across the lifecourse and risk of breast cancer in African American women, the Carolina Breast Cancer Study. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr C84. doi:10.1158/1538-7755.DISP13-C84