Atypical Hyperplasia !of the Breast

Jay Lee, Ariel Oppong, Rebecca Gray

Hyperplasia

Rapid cell proliferation

Tissue engorgement

Four categories

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

Hyperplasia

Simple Complex

Usual

Atypical

n/a

Breast Anatomy

Female reproductive accessory

External Anatomy

nipple

areola

Internal Anatomy

fatty tissue

milk ducts

mammary glands

Breast Anatomy

lobules

alveoli

cubiodal tissue

mammary glands

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

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

SCREENING:MAMMOGRAMS

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

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.

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

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

Estrogen

Modulate genes involved with breast development, regulation of menstrual cycle.

Prolonged exposure increases incidence of breast cancer and various uterine lesions

Nonetheless some women still get Breast Cancer

Potential Treatment Options:

There are preventive treatments, non invasive and invasive methods:

Estrogen Receptors: ER and ER

Ligand-dependent nuclear receptors ER and ER have high anities to estradiol which causes eects within cells.9

Schematic of estrogen and its regulatory function in target cells

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

Tamoxifen

Most widely used SERM antiestrogen for management of breast cancer.

Blocks action of estrogen in cancerous cells.4

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

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.

Something particular about Maine Medical Center:

Maine Medical has recently implemented the use of Radioactive

Seed Localization

Health Care Disparities

Socio-economic

Racial

Geographical

Amongst Citizens, Aliens, Permanent Residents etc.

Employed/ unemployed

Racial Disparities in Health Outcomes for Black Women in Memphis Tennessee

Based on Data from: 2014 Racial Disparity inBreast Cancer Mortality Study11

Racial Disparities are not Specific to Memphis: 11

Racial Disparities in Health Outcomes for Black Women in Houston, Texas

Based on Data from: 2014 Racial Disparity inBreast Cancer Mortality Study11

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

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.

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

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.

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.

Imageshttp://www.darngoodlemonade.com/wp-content/uploads/2012/01/

tamoxifen-estrogen.gif