What’s new in Breast Disease

M. Whitney Parnell MD FACSSurgical Associates of Myrtle Beach

Breast and General Surgery

Dense Breasts ABUS 3-D Mammography BRCA1 BRCA2 and beyond Prophylactic Surgery Cancer Sub-typing (oncotype

DX/Mammoprint)

Hot topics

What does it mean to say dense breasts?Who has dense breasts?Are women with dense breasts at increased risk of developing cancer?What should we do differently?Legislation

Dense Breasts

Breast Anatomy

Fat and glandular tissue More glandular

tissue=denser breast Denser the breasts the

whiter the mammogram Mammogram may miss

up to 40% of cancers in dense breasts

Dense Breasts

Age Hormone levels Genetics Age at first

pregnancy #of pregnancies HRT

Mammograpy’s dirty little secret

Up to 40% of cancer can be missed on standard mammography in dense breasts !

Type 1—mostly fatty replaced Type 2 Average breast tissue 25-50%

Type 3 Heterogenously dense 50-75% Type 4 Extremely dense >75% dense tissue

Dense breast Classifications

Dense Breast Classifications

Why Mammography?

Inexpensive Safe (low radiation) Accessible Sensitive and Specific Effective in reducing

mortality from Breast Cancer

Since 1990’s there has been a decrease in mortality from breast cancer 2.2%/year due to screening mammography

Most frequent dx non-skin cancer in Women 226,870 new cases/yr in US 63,000 new cases of DCIS 40,000 women die annually of breast cancer Second leading cause of cancer death in

women

Breast Cancer Stats

Breast Cancer Risk Factors

Early menarche Late Menopause Nulliparous HRT Post-menopausal obesity ETOH Breast Density

Dense breast are an independent risk cancer for cancer development

Mult retrospective studies show the odds ratios for developing breast cancer in the least dense compared with the densest breast ranges from 1.9-6.0 (ave 4.0) Harvey et al. Radiology 2004

Dense breasts=more Cancer?

Breast cancer is a progressive disease and early detection offers women an opportunity to halt the natural evolution of the cancer, increases her treatment options, and ultimately saves lives.

Early Detection

Mammogram is still the gold standard for screening and it is an invaluable tool— Assessing interval change Architectural distortions Calcifications (i.e. DCIS—stage 0)

Why get a mammogram if I have dense breasts?

Breast Ultrasound MRI Digital breast tomosynthesis

Other Imaging Modalities

Safe—no radiation Technologic advancements have improved

resolution Breast density is a non-issue Easy to perform Well tolerated by patient Invaluable asset to mammography

Ultrasound

High risk women with dense breasts Improved cancer detection 13-28%

Most cancers were early stage invasive node negative cancer

Kolbe et al Radiology 2002 ACRIN 6666; JAMA 2008

Improved Cancer Detection

Connecticut was first 2009—Public Act 09-41

"If your mammogram demonstrates that you have dense breast tissue, which could hide small abnormalities, you might benefit from supplementary screening tests, which can include a breast ultrasound screening or a breast MRI examination, or both, depending on your individual risk factors. A report of your mammography results, which contains information about your breast density, has been sent to your physician's office and you should contact your physician if you have any questions or concerns about this report.

Legislation

South Carolina

Introduce bill Feb 2013 Currently in the House Committee on Labor

Commerce and Industry Sponsored by Senator Joel Lourie

Staffing/Time intensive with low reimbursement

Technician dependent ACR/ACS lack guidelines Adding u/s to mammography increases the

false positive rate 4X—ACRIN 6666: Jama 2008

Breast Ultrasound

Automated Breast Ultrasound Screening 3mins per breast (19mins with u/s tech) Full exam time 15 mins Gives complete 3-D volumetric imaging of

the breast Approved in Sept 2012 “explicitly for breast

cancer screening for asymptomatic women with dense breast tissue.”

97% sensitive when used with mammograpy

ABUS

ACS guidelines Recommended for high risk individuals annually with mammography Known BRCA 1 or 2 mutations First degree family member with genetic

mutation >20% lifetime risk based on Risk analysis models Chest wall radiation ages 10-30 Li-Fraumeni, Cowden and Bannayan-Riely

Ruvalcaba syndromes and first degree relatives

Breast MRI

Expensive Requires contrast agent (baseline creatinine) Uncomfortable (prone position) Lacks insurance mandate Lacks specificity Time in the magnet

Breast MRI

Originally approved as add-on only FDA 2013-approved for use without standard

2-D mammography Provides images of the breast in “slices”

from many different angles Not always covered by insurance Machines cost 2x as much

3-D Mammography

Higher cancer detection rate 4.1 vs 2.9/1000 Less call backs 91 vs 107/1000 Higher bx rate 19.3 vs 18.1 Higher radiation dose (both within safe

limits) Overseas use since 2008—restrict it to

patients with breast problems JAMA. 2014;311(24):2499-2507

3-D Mammography

BRCA1 and BRCA 2 are human genes that produce tumor suppressor proteins

Help repair damaged DNA With mutations of these genes—damaged

DNA is not repaired properly Responsible for 25% of genetic breast cancer

5-10% of all breast cancer 15% of ovarian cancer

Genetics

Genetics

BRCA1

55-65% will develop breast cancer in their lifetime

40% lifetime risk of ovarian cancer

Fallopian tube and peritoneal cancer

Prostate cancer Pancreatic cancer

BRCA2

45% will develop breast cancer in their lifetime

12% lifetime risk of ovarian caner

Linked with male breast cancer

Prostate cancer Pancreatic cancer

Who should get tested?

Breast cancer before 50 Cancer in both breasts Breast and ovarian cancer Personal or family hx of

Male breast cancer

Triple negative breast cancer before age 60

Ashkenazi Jewish heritage and family hx of breast or ovarian cancer

Ovarian cancer before 50

3 rules

Multiple –combination of cancers in the same side of the family

Young--<50 Rare—male breast; triple neg; colorectal or

endometrial cancer with abnormal MSI/IHC;

Identifies elevated risk of 8 cancers by analyzing multiple clincally actionable genes

Retrospective analysis of patients (2006-2013)

6.9% of patients appropriate for HBOC testing also meet Lynch criteria

30% of patients appropriate for Lynch testing also meet HBOC

Expanded panel testing

Previvor - "Cancer previvors" are individuals who are survivors of a predisposition to cancer but who haven’t had the disease. This group includes people who carry a hereditary mutation, a family history of cancer, or some other predisposing factor.

Unaffected carrier

Previvor

Increased awareness Increased inquiries into testing Better lay understanding of genetic testing Prophylactic Mastectomy

Angelina Jolie Effect

Risk reduction of 90+ % Still need to consider prophylactic

oophorectomy Nipple sparing techniques (1% less risk

reduction)

Prophylactic Mastectomy

Molecular profiling

Oncotype Dx Mammoprint

Genomic test of the activity of a group of genes

How cancer may respond to treatment Early stage ER+ breast cancer recurrence

and ?benefit from chemo DCIS—recurrence and or risk of new invasive

cancer developing and ?benefit from XRT

OncotypeDX

Summary

Dense breasts Birads 3 and 4 benefit from annnual screening ultrasound

Consider genetic testing for multiple/ young/rare

Nipple sparing prophylatic mastectomy option

Cancer molecular profiling or subtyping expanding—targeted therapy

Questions?

Questions