Down-Regulation of Messenger Ribonucleic Acid and Protein Levels for Estrogen Receptors by Phorbol Ester and Calcium in MCF7 Cells
Institute of Medical Biochemistry, University of Oslo, P.O. Box 1112, Blindern, 0317 Oslo 3, Norway.
Treatment of MCF-7 cells, a human mammary carcinoma cell line, with phorbol ester... more
Treatment of MCF-7 cells, a human mammary carcinoma cell line, with phorbol ester [12-O-tetradecanoylphorbol-13-acetate (TPA)] or calcium ionophore (A23187) was associated with striking effects on levels of estrogen receptor (ER) mRNA, specific binding of 17β-[3H]estradiol ([3H]E2), and immunoreactive ER.
TPA (10−7 M) caused a time-dependent reduction of ER mRNA which was below the level of detection after 9 h. Similar effects of TPA appeared at levels of specific binding of [3H]E2 as well as immunoreactive ER. In contrast, TPA induced an increase in mRNA for β-actin. Incubation of MCF-7 cells with increasing concentrations of TPA (1011-10−7 M) was associated with biphasic effects on ER mRNA and proteins. Levels of immunoreactive progesterone receptors (PR) were induced by E2 (10−9 M) in a time-dependent manner. In the presence of TPA (10−7 M), where ER levels were suppressed, no induction of PR was observed.
Removal of TPA (10−7 M) after 10 h (ER mRNA) or 22 h (ER proteins) of treatment was associated with a continued suppression of both mRNA and protein levels during the entire incubation period (48 h).
Treatment with A23187 (2 × 10−7 M) also caused a timedependent down-regulation of levels of ER mRNA and proteins. These effects occurred somewhat more slowly than those of TPA. Levels of β-actin mRNA were not changed by this treatment.
These results indicate that changes in estrogen sensitivity are mediated by calcium-dependent protein kinases in human mammary carcinoma MCF-7 cells.
Download (.pdf) Autologous Down-Regulation of Messenger Ribonucleic Acid and Protein Levels for Estrogen Receptors in MCF7 Cells: An Inverse Correlation to Progesterone Receptor Levels
Institute of Medical Biochemistry, University of Oslo, P.O. Box 1112 Blindern, N-0317 Oslo 3, Norway.
In the present study we have examined the effects of estradiol on mRNA levels for estrogen (ER) and progesterone... more
In the present study we have examined the effects of estradiol on mRNA levels for estrogen (ER) and progesterone receptors (PR) in the estrogen-dependent mammary carcinoma MCF-7 cell line. The changes in ER immunoactivity and specific binding of [3H]R5020 were also assessed.
Estradiol (10-7 M) caused a transient and time-dependent reduction of the level of mRNA for ER, with a maximal effect (30-40% of control; n = 3) after 72 h. This was associated with a similar decrease in ER immunoactivity. Further treatment (96 and 120 h) revealed a return of ER mRNA to control values, whereas the ER immunoactivity remained depressed.
The effect on the mRNA level for PR gave almost the inverse curve. Initially (24-72 h), we observed a pronounced increase in this mRNA, with a maximal effect (6-7 times the control value; n = 3) after 72 h. Treatment beyond 72 h was associated with a gradual return of mRNA for PR toward the control level. The variation in specific binding of [3H]R5020 revealed similar changes, except that changes in specific receptor binding were delayed 24 h compared to the levels of mRNA.
Incubation with low concentrations (10-11 and 10-10 M) of estradiol for 72 h was associated with slightly elevated levels of mRNA for ER, whereas higher concentrations gave a dosedependent decrease. The mRNA for PR was biphasically stimulated, with a maximal effect at 10-10-10-8M, where a 10- to 13- fold stimulation was observed. The highest concentration (10-7 M) gave a lower response.
Assessment of concentration-induced variations in protein receptor levels of ER and PR reflected the effects of estradiol on their mRNAs. Low concentrations of estradiol slightly enhanced the ER level, whereas high concentrations clearly reduced ER immunoactivity. The PR level was stimulated by all concentrations used, and 10-8 M estradiol raised the PR level more than 11-fold.
Our results indicate autologous regulation of estrogen receptor gene transcripts and proteins and a clear induction of PR mRNA and receptor proteins by estradiol. (Endocrinology 124: 2577-2583, 1989)
Topological analysis of gene expression arrays identifies high risk molecular subtypes in breast cancer.
Arsuaga J, Baas N, DeWoskin D, Mizuno H, Pankov A, Park C. Applicable Algebra in Engineering, Communication and Computing. 2012, 23:3-15.
Genomic technologies measure thousands of molecular signals with the goal of understanding complex biological... more Genomic technologies measure thousands of molecular signals with the goal of understanding complex biological processes. In cancer these molecular signals have been used to characterize disease subtypes, signaling pathways and to identify subsets of patients with specific prognosis. However molecular signals for any disease type are so vast and complex that novel mathematical approaches are required for further analyses. Persistent and computational homology provide a new method for these analyses. In our previous work we presented a new homology-based supervised classification method to identify copy number aberrations from comparative genomic hybridization arrays. In this work we first propose a theoretical framework for our classification method and second we extend our analysis to gene expression data. We analyze a published breast cancer data set and find that that our method can distinguish most, but not all, different breast cancer subtypes. This result suggests that specific relationships between genes, captured by our algorithm, help distinguish between breast cancer subtypes. We propose that topological methods can be used for the classification and clustering of gene expression profiles.
Working for the Cure: Challenging Pink Ribbon Activism
Published in Configuring Health Consumers: Health Work and the Imperative of Personal Responsibility. Eds. R. Harris, N. Wathen, S. Wyatt. Amsterdam: Palgrave Macmillan, 2010: 140-159.
Captured and branded in the highly recognizable image of the pink ribbon, the politics of breast cancer at the start... more
Captured and branded in the highly recognizable image of the pink ribbon, the politics of breast cancer at the start of the 21st century is markedly hopeful (given the grim statistics) and surprisingly compliant with the medical establishment’s defined health goals and approaches to addressing the breast cancer epidemic. In keeping with this volume’s theme of “Working to be Healthy”, this chapter examines and evaluates how the pink ribbon message has shaped and organized social response to breast cancer. The work in question is “healthwork”, a term found in the critical health literature denoting the active and purposeful work that people do to look after their health (Mykhalovskiy and McCoy, 2002). Healthwork analysis tends to focus on personal care practices—taking medicines, dealing with healthcare practitioners, informal care-giving, health information seeking, etc.—that are then subject to examination of how those individual actions invite extended relations of governance and ruling (Mykhalovskiy, McCoy and Bresalier, 2004). In this examination of breast cancer campaigns, the same analytic concern with governance is taken, but the health-related work is extended beyond personal care and self-surveillance to also include the volunteer work done by many concerned citizens in their contributions of time, energy, and money to support campaigns for the cure.
In this chapter, I argue that while the appropriation of the language and themes of the early women’s health movement frames pink ribbon activism as a highly personal, emancipatory, and socially-responsible individual effort, this brand of breast cancer activism instead serves to fund a limited biomedical research agenda that is largely shielded from public scrutiny. This agenda has been universalized through endearing “hero” narratives of personal struggle that inspire civic engagement by complicit consumers rather than critical activists. Pink ribbon activism problematically diverges from the women’s health movement’s demand for participation in setting the research agenda and determining treatment strategies. This neglect is troubling, given that breast cancer discourse is so fraught with contested knowledge claims regarding disease aetiology, prevention, and treatment. While the pink ribbon message offers hope and optimism, it does so by suppressing many counterclaims, disputes, and ambiguities surrounding the problem of breast cancer. Instead of soft “pink”, a more critical social response to breast cancer is needed in order to ensure women’s informed participation in addressing this serious challenge to women’s health.
Lapatinib and trastuzumab in combination with an aromatase inhibitor for the first-line treatment of metastatic hormone receptorpositive breast cancer which over-expresses human epidermal growth factor 2 (HER2): a systematic review and economic analysis
Co-authored with Bagust, A. Boland, A. Dickson, R. Dundar, Y. Moonan, M. Oyee, J. Blundell, M. Davis, H. Armstrong, A. Thorp, N.
BACKGROUND:
Breast cancer is the uncontrolled, abnormal growth of malignant breast tissue affecting... more
BACKGROUND:
Breast cancer is the uncontrolled, abnormal growth of malignant breast tissue affecting predominantly women. Metastatic breast cancer (mBC) is an advanced stage of the disease when the disease has spread beyond the original organ. Hormone receptor status and human epidermal growth factor 2 (HER2) status are two predictive factors that are taken into consideration when estimating the prognosis of patients with breast cancer.
OBJECTIVES:
To review the clinical effectiveness and cost-effectiveness evidence base for lapatinib (LAP) in combination with an aromatase inhibitor (AI) and trastuzumab (TRA) in combination with an AI for the first-line treatment of patients who have hormone receptor-positive (HR+)/human epidermal growth factor 2-positive (HER2+) mBC.
DATA SOURCES:
Relevant electronic databases and websites, including MEDLINE, EMBASE and the Cochrane Library, were searched until May 2010. Further data were derived from the manufacturers' submissions for LAP + AI and TRA + AI.
REVIEW METHODS:
A systematic review of the clinical effectiveness and cost-effectiveness of LAP + AI and TRA + AI was undertaken. As it was deemed inappropriate to compare LAP + AI with TRA + AI, two separate assessments of cost-effectiveness versus AIs alone were undertaken.
RESULTS:
Three trials were included in the systematic review [the patient populations of the efficacy and safety of lapatinib combined with letrozole (EGF30008) trial, the efficacy and safety of trastuzumab combined with anastrozole (TAnDEM) trial and the efficacy and safety of letrozole combined with trastuzumab (eLEcTRA) trial]. As a result of differences in the exclusion criteria and because one trial was halted prematurely, comparisons across trials were believed to be inappropriate and meta-analysis was not possible. Individually, however, the findings from the trials all suggest that LAP + AI or TRA + AI results in improved progression-free survival and/or time to progression when compared with AIs alone. The trials do not show a statistically significant benefit in terms of overall survival. Two separate economic analyses were conducted based on the completed trials; neither LAP + AI nor TRA + AI was found to be cost-effective when compared with AI monotherapy.
LIMITATIONS:
Because of differences in the EGF30008 and the TAnDEM trials, the Assessment Group believes the indirect comparisons analyses conducted by the manufacturers are inappropriate and, for the same reason, chooses not to compare LAP + AI with TRA + AI in an economic evaluation.
CONCLUSIONS:
LAP + AI and TRA + AI appear to be clinically more effective than AI monotherapy, but neither is cost-effective compared with AIs alone. It was not possible to compare LAP + AI with TRA + AI. Future research should include research into treating mBC in the HR+/HER2+ population who are not TRA (or LAP) naive and into comparing the clinical effectiveness of AIs as monotherapy in patients with HER2+ and human epidermal growth factor 2-negative breast cancer.
FUNDING:
The National Institute for Health Research Technology Assessment programme.
The clinical effectiveness and costeffectiveness of genotyping for CYP2D6 for the management of women with breast cancer treated with tamoxifen: A systematic review
Co-authored with Saborido, C. M. Payne, K. Boland, A. Dickson, R. Dundar, Y. Santander, A. F. Howell, S. Newman, W. Oyee, J. Walley, T.
Background: Breast cancer is the most common cancer affecting women in the UK. Tamoxifen (TAM) is considered as the... more Background: Breast cancer is the most common cancer affecting women in the UK. Tamoxifen (TAM) is considered as the standard of care for many women with oestrogen receptor positive breast cancer. However, wide variability in the response of individuals to drugs at the same doses may occur, which may be a result of interindividual genetic differences (pharmacogenetics). TAM is known to be metabolised to its active metabolites N-desmethyl TAM and 4-hydroxytamoxifen by a number of CYP450 enzymes, including CYP2D6, CYP3A4, CYP2C9, CYP2C19 and CYP2B6. N-desmethyl TAM is further metabolised to endoxifen by CYP2D6. Endoxifen, which is also formed via the action of CYP2D6, is 30- to 100-fold more potent than TAM in suppressing oestrogen-dependent cell proliferation, and is considered an entity responsible for significant pharmacological effects of TAM. Thus, an association between the cytochrome P450 2D6 (CYP2D6) genotype and phenotype (expected drug effects) is believed to exist and it has been postulated that CYP2D6 testing may play a role in optimising an individual's adjuvant hormonal treatment. Objectives: To determine whether or not testing for cytochrome P450 2D6 (CYP2D6) polymorphisms in women with early hormone receptor positive breast cancer leads to improvement in outcomes, is useful for health decision-making and is a cost-effective use of health-care resources. Data sources: Relevant electronic databases and websites including MEDLINE, EMBASE and HuGENet™ [Centers for Disease Control and Prevention (Office of Public Health Genomics), Human Genome Epidemiology Network] were searched until July 2009. Further studies that became known to the authors via relevant conferences or e-mail alerts from an automatically updated search of the Scopus database were also included as the review progressed, up to March 2010. Review methods: A systematic review of the clinical effectiveness and cost-effectiveness of CYP2D6 testing was undertaken. As it was not possible to conduct meta-analyses, data were extracted into structured tables and narratively discussed. An exploratory analysis of sensitivity and specificity was undertaken. A review of economic evaluations and models of CYP2D6 testing for patients treated with TAM was also carried out. Results: A total of 25 cohorts were identified which examined clinical efficacy (overall survival and relapse/recurrence), adverse events and endoxifen plasma concentrations by genotype/phenotype. Significantly, six cohorts suggest extensive metabolisers (Ems) appear to have better outcomes than either poor metabolisers (PMs) or PMs + intermediate metabolisers in terms of relapse/recurrence; however, three cohorts report apparently poorer outcomes for EMs (albeit not statistically significant). There was heterogeneity across the studies in terms of the patient population, alleles tested and outcomes used and defined. One decision model proposing a strategy for CYP2D6 testing for TAM was identified, but this was not suitable for developing a model to examine the costeffectiveness of CYP2D6 testing. It was not possible to produce a de novo model because of a lack of data to populate it. Conclusion: This is a relatively new area of research that is evolving rapidly and, although international consortia are collaborating, the data are limited and conflicting. Therefore, it is not possible to recommend pharmacogenetic testing in this patient population. Future research needs to focus on which alleles (including, or in addition to, those related to CYP2D6) reflect patient response, the link between endoxifen levels and clinical outcomes, and the appropriate pathways for implementation of such pharmacogenetic testing in patient care pathways. FUNDING: The National Institute for Health Research Health Technology Assessment programme.
Vilhauer, R.P., McClintock, M.K., & Matthews, A. K. (2010). Online support groups for women with metastatic breast cancer: a feasibility pilot study. Journal of Psychosocial Oncology 28(5): 560-586.
Contact vilhauerr@felician.edu for the manuscript.
This study evaluates the feasibility and acceptability of an online peer support group intervention for women with... more This study evaluates the feasibility and acceptability of an online peer support group intervention for women with metastatic breast cancer (MBC). Feasibility, participation rates, participant satisfaction, and preliminary outcomes are examined from a 1999 to 2000 study of online peer support groups for women with MBC. Thirty women with MBC were randomly assigned to either an immediate online support condition or a waitlisted control condition. For practical and ethical reasons, the waitlist period was limited to 2 months. Six monthly assessments were collected using standardized measurement instruments. Intervention retention rates (73%), assessment completion rates (range = 100%-86% in retained participants) and support group participation (M = 5.9 days per week) were high compared to other published studies on this population. Reported satisfaction with the intervention was also high. An online support intervention study is feasible using a waitlist control. Despite the feasibility and acceptability of the study procedures, the study design and small sample size precluded definitive conclusions about intervention effectiveness. As such, study procedures should be replicated with a larger more representative sample to examine the effectiveness of the intervention.
Vilhauer, R.P. (2011). ‘Them’ and ‘us’: the experiences of women with metastatic disease in mixed-stage versus stage-specific breast cancer support groups. Psychology & Health, 26 (6): 781-797.
Contact vilhauerr@felician.edu for the manuscript
The objective of this study was to explore the experiences of women with metastatic breast cancer (MBC) in mixed-stage... more The objective of this study was to explore the experiences of women with metastatic breast cancer (MBC) in mixed-stage and stage-specific groups. Interpretative phenomenological analysis (IPA) was used to examine 15 interviews from eight women with MBC. The interviewees felt that their experiences were very much different from those of women with primary breast cancer (BC), because of their different prognoses. In mixed-stage groups, the interviewees described feeling silenced, marginalised and helpless. They did not receive support in these groups because survivors of primary BC are often afraid to face the idea of metastasis. In stage-specific MBC groups, on the other hand, women were able to talk openly and were understood by others with whom they identified. They became more informed about issues related to their illness. Seeing others living well despite MBC made them feel more hopeful. Although there are some disadvantages of participating in stage-specific groups, the findings suggest that, overall, stage-specific groups are more helpful to women with MBC than mixed-stage groups. These findings have implications for the provision of group support for this population.
Vilhauer, R.P. (2008). A qualitative study of the experiences of women with metastatic breast cancer. Palliative and Supportive Care 6(3): 249-258.
Contact vilhauerr@felician.edu for the manuscript.
ABSTRACT
Objective: My objective was to investigate the experiences of women diagnosed with... more
ABSTRACT
Objective: My objective was to investigate the experiences of women diagnosed with metastatic breast cancer.
Method: I did a qualitative study based on interview data. Fourteen women with metastatic breast cancer were recruited into a larger study of online support group use. Participants were interviewed by phone.
Results: The women indicated that they experience distress because of concerns about body image, declines in aspects of their sexual lives, and worries about the effect of stress on their illness. The stress that worries these women comes from fear of dying, fear of disease progression and debilitation, the loss of their future, and practical concerns. The women were also likely to experience a decline in daily activity after being diagnosed with metastatic disease. They become less active because of the physical symptoms of the illness and the side effects of treatments, the medicalization of their lifestyle, their desire to avoid stressful situations, the constraints imposed by their social world, and the need to maintain disability benefits. Although women are often in need of emotional and material support from others after they are diagnosed, social support can decrease, both because women find it difficult to be open about the difficulties they face and because the responses of others are not adequately supportive. Distress and declines in daily activity and social support can feed into each other to create a vicious circle.
Significance of results: This paper makes a significant contribution to the literature by providing a rich description of how metastatic breast cancer affects women. Further research, with more diverse samples, is needed in this understudied area.
Fat Intake and Its Relationship with Pre-and Post-menopausal Breast Cancer Risk: a Case-control Study in Malaysia.
Background: Fat intake has been shown to play a role in the etiology of breast cancer, but the findings have been... more Background: Fat intake has been shown to play a role in the etiology of breast cancer, but the findings have been inconsistent. Objective: To assess the association of premenopausal and postmenopausal breast cancer risk with fat and fat subtypes intake. Methodology: This is a population based case-control study conducted in Kuala Lumpur, Malaysia from January 2006 to December 2007. Food intake pattern was collected from 382 breast cancer patients and 382 control group via an interviewer-administered food frequency questionnaire. Logistic regression was used to compute odds ratios (OR) with 95% confidence intervals (CI) and a broad range of potential confounders was included in analysis. Results: This study showed that both premenopausal and postmenopausal breast cancer risk did not increase significantly with greater intake of total fat [quartile (Q) 4 versus Q1 OR=0.76, 95% CI, 0.23-2.45 and OR=1.36, 95% CI, 0.30-3.12], saturated fat (ORQ4 to Q1=1.43, 95% CI, 0.51-3.98 and ORQ4 to Q1=1.75, 95% CI, 0.62-3.40), monounsaturated fat (ORQ4 to Q1=0.96, 95% CI, 0.34-1.72 and ORQ4 to Q1=1.74, 95% CI, 0.22-2.79), polyunsaturated fat (ORQ4 to Q1=0.64, 95% CI, 0.23-1.73 and ORQ4 to Q1=0.74, 95% CI, 0.39-1.81), n-3 polyunsaturated fat (ORQ4 to Q1=1.10, 95% CI, 0.49-2.48 and ORQ4 to Q1=0.78, 95% CI, 0.28-2.18), n-6 polyunsaturated fat (ORQ4 to Q1=0.67, 95% CI, 0.24-1.84 and ORQ4 to Q1=0.71, 95% CI, 0.29-1.04) or energy intake (ORQ4 to Q1=1.52, 95% CI, 0.68-3.38 and ORQ4 to Q1=2.21, 95% CI, 0.93-3.36). Conclusion: Total fat and fat subtypes were not associated with pre- and postmenopausal breast cancer risk after controlling for age, other breast cancer risk factors and energy intake. Despite the lack of association, the effects of total fat and fat subtypes intake during premenopausal years towards postmenopausal breast cancer risk still warrant investigation.
Dietary Changes Among Breast Cancer Patients in Malaysia
BACKGROUND: Breast cancer patients often show an interest in making dietary changes after diagnosis of breast cancer... more
BACKGROUND: Breast cancer patients often show an interest in making dietary changes after diagnosis of breast cancer in order to improve their health condition and prevent cancer recurrence.
OBJECTIVE: The objective of the study was to determine changes in dietary intake 2 years after diagnosis among breast cancer patients.
METHODS: One hundred sixteen subjects were asked to complete a semiquantitative food frequency questionnaire, diet recalls, and dietary changes questionnaire to assess dietary intake before and after diagnosis. The information on sociodemographic background, cancer treatment history, and anthropometric indices was also collected.
RESULTS: Seventy-two subjects considered diet as a contributing factor to breast cancer, and 67 subjects changed their dietary habits after breast cancer diagnosis. The reasons for changes in diet were physician and dietitian advice and desire to cure cancer. The sources of information were derived from their physician, mass media, and family members. Total energy, protein, total fat, fatty acids, and vitamin E intake were significantly decreased after diagnosis. Meanwhile, the intake of β-carotene and vitamin C increased significantly after diagnosis. The changes included reduction in red meat, seafood, noodles, and poultry intake. An increased consumption of fruits, vegetables, fish, low-fat milk, and soy products was observed. The subjects tended to lower high-fat foods intake and started to eat more fruits and vegetables.
CONCLUSION: Breast cancer patients had changed to a healthier diet after breast cancer diagnosis, although the changes made were small.
IMPLICATIONS FOR PRACTICE: This will be helpful to dietitians in providing a better understanding of good eating habits that will maintain patients' health after breast cancer diagnosis.
Breast cancer delay: A grounded model of help-seeking behaviour
Social Science and Medicine, 2011; Volume 72, Issue 7, Pages 1096-1104.
Coauthoured with Claudia Infante Castañeda.
The conventional definition and classifications of breast cancer delay are based on arbitrary empirical time cut-offs.... more The conventional definition and classifications of breast cancer delay are based on arbitrary empirical time cut-offs. In general, studies of cancer delay are based on these traditional definitions of patient and provider delay and are essentially atheoretical. If we aim to better understand delay, a reconsideration of its traditional conceptualisation and study methods is warranted. We propose a multidimensional model of breast cancer delay grounded in data from in-depth interviews with symptomatic patients and nested in the theory of illness behaviour. Our results show that delay prior to the first encounter with health services has to do with more than simply the patient as an individual, and delay posterior to this encounter is not due only to the health care providers. In fact, delay is a result of the interplay between the patient’s socio-cultural context, individual characteristics that influence symptom interpretation and decision-making, interaction with the social network and types of support obtained, and aspects of the local health services. Future research on cancer delay should approach the problem integrally, taking into account the diverse dimensions involved.
Is breast cancer delay really the patient's fault?
Electronic book chapter in: Relational Concepts in Medicine. Edited by Mario Deng, Federico Raia and Maria Vaccarella. ISBN: 978-1-84888-073-3
Breast cancer delay is defined as more than three months between symptom discovery and the beginning of definitive... more Breast cancer delay is defined as more than three months between symptom discovery and the beginning of definitive treatment. It has been artificially divided in two problems: patient delay -between symptom discovery and the first medical consultation- and provider delay -between the first medical consultation and the beginning of treatment-. Research to date has focused on the former and has attributed delay mainly to patients’ untimely medical attention-seeking behaviour. The present study uses mixed-methods in order to quantify delay intervals and explain the way that social and health services factors influence delayed medical attention of breast cancer patients treated at the National Cancer Institute of Mexico. Seventeen in-depth interviews were done to identify sources of delay from the patients’ perspective. A questionnaire was developed to quantify delay and applied as a pilot study to 125 patients. The time from symptom discovery to the beginning of cancer treatment had a median value of 247.5 days. There was no delay in only 5.3% cases. There was patient delay in 23.5% cases while there was provider delay greater than three months in 80% patients. The main factors contributing to delay were socioeconomic factors, health services access barriers and medical diagnosis errors.
Delay of medical care for symptomatic breast cancer: A literature review
Published in Salud Pública de México, 2009.
The purpose of this paper is to organize and summarize
existing information on delayed medical attention for... more
The purpose of this paper is to organize and summarize
existing information on delayed medical attention for women
with breast cancer and identify research needs in this area.
This review is organized in six parts: I) origins and permanence
of the message “do not delay” medical attention for potential
cancer symptoms; II) definition and classification of breast
cancer delay; III) impact of delay on breast cancer prognosis;
IV) factors related to breast cancer delay and the ways these
have been studied; V) the study of breast cancer delay in
Mexico; and VI) directions for future research in developing
countries, with a special focus on Mexico. We point out the
need of a more integral study of delay that takes into account
socio-structural and health services factors, in order to find
modifiable factors towards which political actions should
be directed to improve breast cancer medical attention in
underdeveloped countries.
