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Atypical Hyperplasia !of the Breast
Jay Lee, Ariel Oppong, Rebecca Gray
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Hyperplasia
Rapid cell proliferation
Tissue engorgement
Four categories
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Hyperplasia
Simple Complex
Usual Atypical
Endometrium contains hyperplastic
colony
Hyperplastic colony reaches beyond
endometrium
Hyperplastic cells are healthy in shape and
function
Hyperplastic cells serve no function and
appear deformed
Four categories
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Hyperplasia
Simple Complex
Usual
Atypical
n/a
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Breast Anatomy
Female reproductive accessory
External Anatomy
nipple
areola
Internal Anatomy
fatty tissue
milk ducts
mammary glands
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Breast Anatomy
lobules
alveoli
cubiodal tissue
mammary glands
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Hyperplasia of the Breast
Occurs in lobules or milk ducts
Harmless unless complex, atypical
Precursor to carcinoma in breast
Premalignant rapid, clustered proliferation nonuniform appearance cells lack function
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Prevention
Three tests are used by health care providers to screen for breast cancer:
1.Mammogram
2.Clinical Breast Exam
3.Magnetic Resonance Imaging (MRI) for High Risk Women
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SCREENING:MAMMOGRAMS
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SCREENING-CLINICAL BREAST EXAMINATION
Assess Patients history and its contribution to patient risk
Complete Lymph Node exam
Visual Breast Examination: any abnormalities
Check for Palpitations on hands and pressure points
Document findings and record plan of action
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SCREENING:MAGNETIC RESONANCE IMAGINGThe American Cancer Society :
Most of the published guidelines state only relative risk data for atypical hyperplasia or a lower lifetime risk, such as 15 %, which does not qualify them for screening MRI.
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NEW ENGLAND JOURNAL OF MEDICINE: SPECIAL 2015 REPORT
Atypical Hyperplasia of the Breast- Risk Assessment and Management
Options
Articles Conclusions: Currently, atypical hyperplasia confers an absolute risk
of later breast cancer of 30%1
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25 Guidelines for high-risk women should be updated1 :
To include women w/ atypical hyperplasia; screening MRI should be considered an option for them
Education regarding chemoprevention
Need more quality-control studies to ensure the application of standardized pathological criteria.
ARTICLE RECOMMENDATIONS:
qidentify new biomarkers that can predict dierent subtypes of breast cancer and varying time frames of risk
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Estrogen
Modulate genes involved with breast development, regulation of menstrual cycle.
Prolonged exposure increases incidence of breast cancer and various uterine lesions
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Nonetheless some women still get Breast Cancer
Potential Treatment Options:
There are preventive treatments, non invasive and invasive methods:
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Estrogen Receptors: ER and ER
Ligand-dependent nuclear receptors ER and ER have high anities to estradiol which causes eects within cells.9
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Schematic of estrogen and its regulatory function in target cells
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Selective Estrogen Receptor Modulators (SERM)
SERMs are a class of compounds which can act in some tissues as estrogens (agonist), but block estrogen actions in others (antagonist).Dierent SERMs induce distinct structural changes in the receptors. 5
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Tamoxifen
Most widely used SERM antiestrogen for management of breast cancer.
Blocks action of estrogen in cancerous cells.4
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Raloxifene
ER antagonist in breast and agonist in bone, but is not an agonist in the uterus.2
However, there is increased risk of venous thromboembolism and fatal stroke.11
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SERMs
Does not alleviate hot flushes and night sweats associated with estrogen loss.SERMs are infrequently prescribed and used. For patients, there were documentations of reluctance.
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Something particular about Maine Medical Center:
Maine Medical has recently implemented the use of Radioactive
Seed Localization
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Health Care Disparities
Socio-economic
Racial
Geographical
Amongst Citizens, Aliens, Permanent Residents etc.
Employed/ unemployed
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Racial Disparities in Health Outcomes for Black Women in Memphis Tennessee
Based on Data from: 2014 Racial Disparity inBreast Cancer Mortality Study11
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Racial Disparities are not Specific to Memphis: 11
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Racial Disparities in Health Outcomes for Black Women in Houston, Texas
Based on Data from: 2014 Racial Disparity inBreast Cancer Mortality Study11
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Theories on the Origins of the Disparity
Four Key Factors that led to this racial disparity
Dierential Access to Screening,
Quality of the screening process
Access to Treatment
Quality of Treatment
NOTE: Although the death rates declined for both white and black women in the United States as a whole over this time period, the white death rate decreased twice as much as the black death rate11
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For the Curious Biology enthusiasts.YES- There is a dierence in incidence rates BUT.
Mortality is 77% higher among African American women compared w/ white women (11.0 vs 6.3 deaths per 100 000).
Breast cancer in African American women: higher grade, later stage at diagnosis, and worse survival even after controlling for stage at diagnosis5.
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OTHER Examples of Disparities
Breast cancer is the main cause of cancer deaths for Hispanic women.10
Invasive breast cancer (BC) is one of the predominant diseases in older women. 9
In Los Angeles County, advanced Breast cancer diagnosis was more likely in areas that had a larger proportion of minority racial or ethnic groups or low median household income. 9
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Conclusion
Need to implement new screening methods
Need new policies to be enacted to decrease health disparities
Need more education initiatives
Need to stress the powerful conclusions that meta-analyses can provide.
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References1. Hartmann, L. C., Degnim, A. C., Santen, R. J., Dupont, W. D., & Ghosh, K. (2015). Atypical Hyperplasia of the Breast
Risk Assessment and Management Options. New England Journal of Medicine, 372(1), 78-89. 2. Nussey S, Whitehead S. Endocrinology: An Integrated Approach. Oxford: BIOS Scientific Publishers; 2001.
Box 6.54, Selective estrogen receptor modulators 3. Shang, Y. (2006). Molecular mechanisms of oestrogen and SERMs in endometrial carcinogenesis. Nature Reviews
Cancer, 6(5), 360-368.4. Kuiper, G. G., Shughrue, P. J., Merchenthaler, I., & Gustafsson, J. . (1998). The estrogen receptor subtype: a novel
mediator of estrogen action in neuroendocrine systems. Frontiers in neuroendocrinology, 19(4), 253-286.5. Carey, Lisa A., et al. "Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study." Jama 295.21
(2006): 2492-2502.6. Boersma, C., & Mosselman, S. (2000). Estrogen Receptors alpha and beeta Two Receptors of a Kind. Current medicinal
chemistry, 7(5), 561-576.7. Sommer, S., & Fuqua, S. A. (2001, October). Estrogen receptor and breast cancer. In Seminars in cancer biology (Vol. 11,
No. 5, pp. 339-352). Academic Press.8. Murphy, L. C., & Watson, P. (2002). Steroid receptors in human breast tumorigenesis and breast cancer progression.
Biomedicine & pharmacotherapy,56(2), 65-77.9. Kuo, Tzy-Mey, Lee R. Mobley, and Luc Anselin. "Geographic disparities in late-stage breast cancer diagnosis in
California." Health & place 17.1 (2011): 327-334.10. Pagn, J. A., Brown, C. J., Asch, D. A., Armstrong, K., Bastida, E., & Guerra, C. (2012). Health literacy and breast cancer
screening among Mexican American women in South Texas. Journal of Cancer Education, 27(1), 132-137.11. Barrett-Connor, E., Mosca, L., Collins, P., Geiger, M. J., Grady, D., Kornitzer, M., ... & Wenger, N. K. (2006). Eects of
raloxifene on cardiovascular events and breast cancer in postmenopausal women. New England Journal of Medicine, 355(2), 125-137.
12. Hartmann, L. C., Degnim, A. C., Santen, R. J., Dupont, W. D., & Ghosh, K. (2015). Atypical Hyperplasia of the BreastRisk Assessment and Management Options. New England Journal of Medicine, 372(1), 78-89.
13. Deroo, B. J., & Korach, K. S. (2006). Estrogen receptors and human disease.Journal of Clinical Investigation, 116(3), 561-570.
14. Dutertre, M., & Smith, C. L. (2000). Molecular mechanisms of selective estrogen receptor modulator (SERM) action. Journal of Pharmacology and Experimental Therapeutics, 295(2), 431-437.
15. Sestak, I. (2014). Preventative therapies for healthy women at high risk of breast cancer. Cancer management and research, 6, 423.
16. Park, W. C., & Jordan, V. C. (2002). Selective estrogen receptor modulators (SERMS) and their roles in breast cancer prevention. Trends in molecular medicine, 8(2), 82-88.
17. Murphy, L. C., & Watson, P. (2002). Steroid receptors in human breast tumorigenesis and breast cancer progression. Biomedicine & pharmacotherapy,56(2), 65-77.
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