Impact of racial differences in medical care on breast cancer survival: Findings from a large nationwide and retrospective cohort study

Background: No studies have attempted to determine whether nodal surgery utilization, time to initiation and completion of chemotherapy or surveillance mammography impact breast cancer survival. ^ Objectives and Methods: To determine whether receipt of nodal surgery, initiation and completion of chemotherapy, and surveillance mammography impact of racial disparities in survival among breast cancer patients in SEER areas, 1992-2005. ^ Results: Adjusting for nodal surgery did not reduce racial disparities in survival. Patients who initiated chemotherapy more than three months after surgery were 1.8 times more likely to die of breast cancer (95% CI 1.3-2.5) compared to those who initiated chemotherapy less than a month after surgery, even after controlling for known confounders or controlling for race. Despite correcting for chemotherapy initiation and completion and known predictors of outcome, African American women still had worse disease specific survival than their Caucasian counterparts. We found that non-whites underwent surveillance mammography less frequently compared with whites and mammography use during a one- or two-year time interval was associated with a small reduced risk of breast-cancer-specific and all-cause mortality. Women who received a mammogram during a two-year interval could expect the same disease-specific survival benefit or overall survival benefit as women who received a mammogram during a one-year interval. We found that while adjustment for surveillance mammography receipt and physician visits reduced differences in mortality between blacks and whites, these survival disparities were eliminated after adjusting for the number of surveillance mammograms received. ^ Conclusions: The disparities in survival among African American and Hispanic women with breast cancer are not explained by nodal surgery utilization or chemotherapy initiation and chemotherapy completion. Surveillance mammograms, physician visits and number of mammograms received may play a major role in achieving equal outcomes for breast cancer-specific mortality for women diagnosed with primary breast cancer. Racial disparities in all-cause mortality were explained by racial differences in surveillance mammograms to certain degree, but were no longer significant after controlling for differences in comorbidity. Focusing on access to quality care and post treatment surveillance might help achieve national goals to eliminate racial disparities in healthcare and outcomes. ^

Breast cancer risk factors among Mexican-American women

Introduction: The average age of onset of breast cancer among Hispanic women is 50 years, more than a decade earlier than non-Hispanic white women. Age at diagnosis is an important prognostic factor for breast cancer; younger age at onset is more likely to be associated with advanced disease, poorer prognosis, hormone receptor negative breast tumors, and a greater likelihood of hereditary breast cancer. Studies of breast cancer risk factors including reproductive risk factors, family history of breast cancer, and breast cancer subtype have been conducted predominately in non-Hispanic whites. Breast cancer is a heterogeneous disease with the presence of clinically, biologically, and epidemiologically distinct subtypes that also differ with respect to their risk factors. The associations between reproductive risk factors and family history of breast cancer have been well documented in the literature. However, only a few studies have assessed these associations with breast cancer subtype in Hispanic populations. Methods: To assess the associations between reproductive risk factors and family history of breast cancer we conducted three separate studies. First, we conducted a case-control study of 172 Mexican-American breast cancer cases and 344 age matched controls residing in Harris County, TX to assess reproductive and other risk factors. We conducted logistic regression analysis to assess differences in cases and controls adjusted for age at diagnosis and birthplace and then we conducted a multinomial logistic regression analysis to compare reproductive risk factors among the breast tumor subtypes. In a second study, we identified 139 breast cancer patients with a first- or second-degree family history of breast cancer and 298 without a family history from the ELLA Bi-National Breast Cancer Study. In this analysis, we also computed a multinomial logistic regression to evaluate associations between family history of breast cancer and breast cancer subtypes, and logistic regression to estimate associations between breast cancer screening practices with family history of breast cancer. In the final study, we employed a cross-sectional study design in 7279 Mexican-American women in the Mano a Mano Cohort Study. We evaluated associations with family history of breast cancer and breast cancer risk factors including body mass index (BMI), lifestyle factors, migration history, and adherence to American Cancer Society (ACS) guidelines. Results: In the results of our first analyses, reproductive risk factors differed in the magnitude and direction of associations when stratified by age and birthplace among cases and controls. In our second study, family history of breast cancer, and having at least one relative diagnosed at an early age (<50 years) was associated with triple negative breast cancer (TNBC). Mammography prior to receiving a breast cancer diagnosis was associated with family history of breast cancer. In our third study that assessed lifestyle factors, migration history and family history of breast cancer; we found that women with a first-degree family history of breast cancer were more overweight or obese compared with their counterparts without a family history. There was no indication that having a family history contributed to women practicing healthier lifestyle behaviors and/or adhering to the ACS guidelines for cancer prevention. Conclusions: We observed that among Mexican-American women, reproductive risk factors were associated with breast cancer where the woman was born (US or Mexico). Having a family history of breast cancer, especially having either a first- or second-degree relative diagnosed at a younger age, was strongly associated with TNBC subtype. These results are consistent with other published studies in this area. Further, our results indicate that women with strong family histories of breast cancer are more likely to undertake mammography but not to engage in healthier lifestyle behaviors.^

Mechanisms of HER2/{\it neu\/} proto-oncogene overexpression in breast cancer cells

Overexpression and amplification of HER2/neu have been documented in many primary tumors, most notably in breast. Not only do approximately 30% of breast cancer patients carry tumors that overexpress the gene, but those that do generally have shorter overall and disease-free survival times than patients with tumors expressing low levels of HER2/neu. Thus, overexpression of HER2/neu plays an important role in the pathogenesis of breast cancer. We have examined the mechanisms that result in HER2/neu overexpression in breast cancer by using, as a model system, established breast cancer cell lines that express much higher levels of HER2/neu mRNA than normal breast tissue while maintaining a near normal HER2/neu gene copy number. Nuclear run-on experiments indicate that the breast cancer cell lines MDA-MB453, BT483, and BT474 have an increased HER2/neu gene transcription rate. By using HER2/neu promoter-CAT constructs, we have found that the enhanced HER2/neu transcription rate in MDA-MB453 cells is due to activation of the gene in trans, while the enhanced transcription rate in BT483 cells is due to activation of the gene in either trans or cis. In BT474 cells, transcriptional upregulation is primarily due to gene amplification. Since the levels of increased transcription are not as high as the levels of HER2/neu mRNA in any of these three lines, post-transcriptional deregulation that increases HER2/neu expression must also be functioning in these cells. The half-life of HER2/neu mRNA was measured and found to be equivalent in these lines as in a control. Thus, the post-transcriptional deregulation is not increased stability of the HER2/neu transcript.^ Much work has been performed in characterizing the altered trans-acting factor involved in increased HER2/neu transcription in MDA-MB453 cells. Using promoter deletion constructs linked to a reporter gene, the region responsive to this factor was localized in the rat neu promoter. When human HER2/neu promoter constructs were used, the homologous sequence in the human promoter was identified. Furthermore, a number of protein/DNA complexes are detected when these promoter regions are used in gel mobility shift assays. UV-crosslinking experiments indicate DNA-binding proteins of roughly 110 kDa, 70 kDa, and 35 kDa are capable of interacting with the human promoter element. ^

Understanding Mastectomy from a Self Psychology Perspective: The Breast as a Self Object

For many women, if not all, breasts are an important component of bodyself-image; a woman may love them or dislike them, but she is rarely neutral" (Young, 2003, p.152). Breast cancer may be one of the oldest forms of cancer known to humans (American Cancer Society, 2010), and in 2008 in the United States over 182,000 women and almost 2,000 men were diagnosed with some form of breast cancer (American Cancer Society, 2008). In that same year 40,480 women and 450 men died from the disease. While any type of cancer diagnosis can instill a fear of mortality and incapacitation in the recipient, breast cancer holds a special meaning for women because of the significance placed on the breast both personally and societally. Removal of the breast tissue and muscle, or mastectomy, remains one of the primary forms of treatment for this disease. The breast plays an important role in a woman's identity, and the loss of one or both breasts due to breast cancer can have a monumental impact on her sense of self. A mastectomy affectsnot only a woman's relationship with herself, but with her family, friends, and society. It changes her outlook on life, her perception of her roles in the world, and her interest in interacting with others. Exploring these issues is important to understanding how doctors, nurses, mental health professionals, family members and support networks can best assist patients in coping with their illness. This paper attempts to understand the psychological issues and injuriesassociated with mastectomy through the lens of Self Psychology. It postulates that the breast itself is a selfobject for most women, and that its loss results in the fragmentation of the self. I will focus particularly on women between the ages of 25 and 40 years of age, in the marital and parental phases of developmental (Wolf, 1988), as the effect of a mastectomy on body image, sexuality, and genderbased roles such as motherhood has been shown to differ according to the age of the patient, with younger patients experiencing more distress (Ashing-Giwa et al, 2004).

Y-box binding protein 1 (YB-1) relevance in estrogen receptor-positive (ER+) breast cancer

Tese de mestrado, Biologia Molecular e Genética, Universidade de Lisboa, Faculdade de Ciências, 2016

CYP2D6 inherited variation and inhibiting medication use in relation to adverse breast cancer outcomes after tamoxifen therapy

Thesis (Master's)--University of Washington, 2016-06

Changes in survival after breast cancer: improvements in diagnosis or treatment?

We have compared 5-year survival rates in two cohorts of women diagnosed with breast cancer in Brisbane, Australia, between 1981-1984 and 1990-1994. Tumours diagnosed in the early 1990s were significantly smaller and less likely to have nodal involvement than those diagnosed 10 years earlier (P < 0.0001). The size difference was particularly striking for women aged over 50 at diagnosis, those targeted for screening. Five-year survival was greater among women diagnosed in the 1990s (84% vs. 74%; hazard ratio (HR) 0.61, 95% confidence interval (CI) 0.46-0.81). After adjusting for the effects of tumour size and nodal status this difference was reduced, but women diagnosed more recently still showed improved survival (HR 0.75; 95% CI 0.56-1.01) and disease-free survival (HR 0.72; 0.56-0.92) at 5 years. This suggests that both earlier diagnosis and changes in breast cancer treatment have contributed to improved breast cancer survival. (C) 2003 Elsevier Ltd. All rights reserved.

Children's and family needs of young women with advanced breast cancer: A review

This article reviews literature about the impact of advanced breast cancer on children and families. It is clear that the adjustment of the family is influenced by disease stage and maternal adjustment, the needs of the particular child relating closely to their developmental stage. Interventions with children and families to promote adjustment when a parent has advanced cancer are also discussed, including implications for clinical practice.

Educating readers: Breast cancer in Australian women's magazines

Women's magazines in Australia have become increasingly involved in various public health awareness campaigns. In particular, breast cancer has been targeted as an issue for attention. This disease occupies a privileged position in women's magazines, being represented as treatable and survivable with an emphasis on the advocacy of early detection through breast self-examination and screening programs. In this way, women's magazines can be seen to be proactive in serving the public interest of their readers. Information and advice about breast cancer are not limited to medical articles, advice columns and diet pages, but occur, perhaps more accessibly, in feature articles of personal accounts of experiences with breast cancer. This paper looks at coverage of the disease in Australian women's magazines over the last 3 years to see how this role in public health awareness operates. It pays particular attention to illness narratives in feature articles and to stories associated with the magazines' own breast cancer campaigns.

Columnar cell lesions of the breast: The missing link in breast cancer progression? A morphological and molecular analysis

Columnar cell lesions (CCLs) of the breast are a spectrum of lesions that have posed difficulties to pathologists for many years, prompting discussion concerning their biologic and clinical significance. We present a study of CCL in context with hyperplasia of usual type (HUT) and the more advanced lesions ductal carcinoma in situ (DCIS) and invasive ductal carcinoma. A total of 81 lesions from 18 patients were subjected to a comprehensive morphologic review based upon a modified version of Schnitt's classification system for CCL, immunophenotypic analysis (estrogen receptor [ER], progesterone receptor [PgR], Her2/neu, cytokeratin 5/6 [CK5/6], cytokeratin 14 [CK14], E-cadherin, p53) and for the first time, a whole genome molecular analysis by comparative genomic hybridization. Multiple CCLs from 3 patients were studied in particular detail, with topographic information and/or showing a morphologic spectrum of CCL within individual terminal duct lobular units. CCLs were ER an PgR positive, CK5/6 and CK14 negative, exhibit low numbers of genetic alterations and recurrent 16q loss, features that are similar to those of low grade in situ and invasive carcinoma. The molecular genetic profiles closely reflect the degree of proliferation and atypia in CCL, indicating some of these lesions represent both a morphologic and molecular continuum. In addition, overlapping chromosomal alterations between CCL and more advanced lesions within individual terminal duct lobular units suggest a commonality in molecular evolution. These data further support the hypothesis that CCLs are a nonobligate, intermediary step in the development of some forms of low grade in situ and invasive carcinoma. Copyright: © 2005 Lippincott Williams & Wilkins, Inc.

Screening with magnetic resonance imaging and mammography of a UK population at high familial risk of breast cancer: a prospective multicentre cohort study (MARIBS)

Background Women genetically predisposed to breast cancer often develop the disease at a young age when dense breast tissue reduces the sensitivity of X-ray mammography. Our aim was, therefore, to compare contrast enhanced magnetic resonance imaging (CE MRI) with mammography for screening. Methods We did a prospective multicentre cohort study in 649 women aged 35-49 years with a strong family history of breast cancer or a high probability of a BRCA1, BRCA2, or TP53 mutation. We recruited participants from 22 centres in the UK, and offered the women annual screening with CE MRI and mammography for 2-7 years. Findings We diagnosed 35 cancers in the 649 women screened with both mammography and CE MRI (1881 screens): 19 by CE MRI only, six by mammography only, and eight by both, with two interval cases. Sensitivity was significantly higher for CE MRI (77%, 95% CI 60-90) than for mammography (40%, 24-58; p=0.01), and was 94% (81-99) when both methods were used. Specificity was 93% (92-95) for mammography, 81% (80-83) for CE MRI (p

Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype

Purpose: To investigate the proportion of breast cancers arising inpatients with germ line BRCA1 and BRCA2 mutations expressing basal markers and developing predictive tests for identification of high-risk patients. Experimental Design: Histopathologic material from 182 tumors in BRCA1 mutation carriers, 63 BRCA2 carriers, and 109 controls, collected as part of the international Breast Cancer Linkage Consortium were immunohistochemically stained for CK14, CK5/6, CK17, epidermal growth factor receptor (EGFR), and osteonectin. Results: All five basal markers were commoner in BRCA1 tumors than in control tumors (CK14: 61% versus 12%; CK5/6: 58% versus 7%; CK17: 53% versus 10%; osteonectin: 43% versus 19%; EGFR: 67% versus 21%; P < 0.0001 in each case). In a multivariate analysis, CK14, CK5/6, and estrogen receptor (ER) remained significant predictors of BRCA1 carrier status. In contrast, the frequency of basal markers in BRCA2 tumors did not differ significant from controls. Conclusion: The use of cytokeratin staining in combination with ER and morphology provides a more accurate predictor of BRCA1 mutation status than previously available, that may be useful in selecting patients for BRCA1 mutation testing. The high percentage of BRCA1 cases positive for EGFR suggests that specific anti-tyrosine kinase therapy may be of potential benefit in these patients.

The impact of rehabilitation support services on health-related quality of life for women with breast cancer

As the number of women surviving breast cancer increases, with implications for the health system, research into the physical and psychosocial sequelae of the cancer and its treatment is a priority. This research estimated self-reported health-related quality of life (HRQoL) associated with two rehabilitation interventions for breast cancer survivors, compared to a non-intervention group. Women were selected if they received an early home-based physiotherapy intervention (DAART, n = 36) or a group-based exercise and psychosocial intervention (STRETCH, n = 31). Questionnaires on HRQoL, using the Functional Assessment of Cancer Therapy - Breast Cancer plus Arm Morbidity module, were administered at pre-, post-intervention, 6- and 12-months post-diagnosis. Data on a non-intervention group (n = 208) were available 6- and 12-months post-diagnosis. Comparing pre/post-intervention measures, benefits were evident for functional well-being, including reductions in arm morbidity and upper-body disability for participants completing the DAART service at one-to-two months following diagnosis. In contrast, minimal changes were observed between pre/post-intervention measures for the STRETCH group at approximately 4-months post-diagnosis. Overall, mean HRQoL scores (adjusted for age, chemotherapy, hormone therapy, high blood pressure and occupation type) improved gradually across all groups from 6- to 12-months post-diagnosis, and no prominent differences were found. However, this obscured declining HRQoL scores for 20-40% of women at 12 months post-diagnosis, despite receiving supportive care services. Greater awareness and screening for adjustment problems among breast cancer survivors is required throughout the disease trajectory. Early physiotherapy after surgery has the potential for short-term functional, physical and overall HRQoL benefits.

Basal-like breast carcinomas: clinical outcome and response to chemotherapy

Background: Grade-III invasive ductal carcinomas of no special type (IDCs-NST) constitute a heterogeneous group of tumours with different clinical behaviour and response to chemotherapy. As many as 25% of all grade-III IDCs-NST are known to harbour a basal-like phenotype, as defined by gene expression profiling or immunohistochemistry for basal cytokeratins. Patients with basal-like breast carcinomas (BLBC) are reported to have a shorter disease-free and overall survival. Material and methods: A retrospective analysis of 49 patients with BLBC (as defined by basal cytokeratin expression) and 49 controls matched for age, nodal status and grade was carried out. Histological features, immunohistochemical findings for oestrogen receptor (ER), progesterone receptor (PgR) and HER2, and clinical outcome and survival after adjuvant chemotherapy were compared between the two groups. Results: It was more likely for patients with BLBCs to be found negative for ER (p < 0.0001), PgR (p < 0.0001) and HER2 (p < 0.01) than controls. Patients with BLBCs were found to have a significantly higher recurrence rate (p < 0.05) and were associated with significantly shorter disease-free and overall survival (both p, 0.05). In the group of patients who received anthracycline-based adjuvant chemotherapy (BLBC group, n = 47; controls, n = 49), both disease-free and overall survival were found to be significantly shorter in the BLBC group (p < 0.05). Conclusions: BLBCs are a distinct clinical and pathological entity, characterised by high nuclear grade, lack of hormone receptors and HER2 expression and a more aggressive clinical course. Standard adjuvant chemotherapy seems to be less effective in these tumours and new therapeutic approaches are indicated.

Pathological complete response and residual DCIS following neoadjuvant chemotherapy for breast carcinoma

Patients who have no residual invasive cancer following neoadjuvant chemotherapy for breast carcinoma have a better overall survival than those with residual disease. Many classification systems assessing pathological response to neoadjuvant chemotherapy include residual ductal carcinoma in situ (DCIS) only in the definition of pathological complete response. The purpose of this study was to investigate whether patients with residual DCIS only have the same prognosis as those with no residual invasive or in situ disease. A retrospective analysis of a prospectively maintained database identified 435 patients, who received neoadjuvant chemotherapy for operable breast cancer between February 1985 and February 2003. Of these, 30 (7%; 95% CI 5-9%) had no residual invasive disease or DCIS and 20 (5%; CI 3-7%) had residual DCIS only. With a median follow-up of 61 months, there was no statistical difference in disease-free survival, 80% (95% CI 60-90%) in those with no residual invasive or in situ disease and 61% (95% CI 35-80%) in those with DCIS only (P = 0.4). No significant difference in 5-year overall survival was observed, 93% (95% CI 75-98%) in those with no residual invasive or in situ disease and 82% (95% CI 52-94%) in those with DCIS only (P = 0.3). Due to the small number of patients and limited number of events in each group, it is not possible to draw definitive conclusions from this study. Further analyses of other databases are required to confirm our finding of no difference in disease-free and overall survival between patients with residual DCIS and those with no invasive or in situ disease following neoadjuvant chemotherapy for breast cancer.