What is new in Breast Cancer Genetics and other Cancer Genetics for women?

By: Holly L. Thacker, MDHolly Pederson, MD • Posted on October 03, 2019

What is new in Breast Cancer Genetics and other Cancer Genetics for women? What is new in Breast Cancer Genetics and other Cancer Genetics for women?

BRCA1 and BRCA2 Mutations

It has been several years since many of us heard about Ms. Angelina Jolie's bilateral mastectomy (removal of the breasts) and breast reconstruction. She learned she was at a very high lifetime risk for breast cancer due to inheriting the BRCA1 mutation. Since that time, there have been many other inherited cancer syndromes identified. Knowledge is power!

BRCA1 and BRCA2 are autosomal dominant genes, which means someone has a 50/50 chance of inheriting one of these mutations if one of their biological parents has that mutation. And these mutations have high penetrance and can occur via either the mother's or the father's side. Having the bilateral mastectomy surgery reduced Angelina's risk for developing breast cancer by 90-95%. By sharing her personal story, she helped raise awareness.

BRCA1 increases the risk of breast cancer in women, while BRCA2 increases the risk for breast cancer in both women and men. Both BRCA mutations increase the risk for deadly, hard to diagnose (with no good screening tests) ovarian cancer. Angelina also underwent bilateral risk reducing oophorectomy (removal of both ovaries), which reduces the risk for ovarian cancer and overall mortality for other cancers that are associated with these mutations, such as:

  • Pancreatic cancer (BRCA2; and some risk with BRCA1)
  • Prostate cancer (BRCA2; and some risk with BRCA1)
  • Melanoma (BRCA2)
  • Colon Cancer (a small increased risk with BRCA1)

It is important to identify carriers of BRCA mutations EARLY IN LIFE as breast cancer screening begin at the age of 25. The average age of a breast cancer diagnosis is 42, as compared to 62 in the general population. It is important to note that home genetic tests are limited and are not complete and a negative test for BRCA is not reassuring if you are not of Ashkenazi Jewish descent.

Other Inherited Cancer Syndromes That You Should Know About

Lynch Syndrome

While prophylactic risk reducing bilateral mastectomy in a famous actress garners much attention, it is important to note there is another common hereditary cancer syndrome that you and your family should also know about. That is Lynch syndrome (LS). LS is caused by gene mutations in five different mismatch repair genes. Women carrying LS mutations are at increased risk for the following:

Colonoscopy, every 1-2 years beginning at the age of 20-25, reduces colon rectal cancer (CRC) and the risk of dying from the disease. We also can evaluate and treat uterine cancer early with a pelvic ultrasound, office endometrial biopsy and hysterectomy. It is unfortunate that many young women with either CRC and/or uterine cancer are not identified as candidates to be tested for Lynch syndrome. These latter 2 cancers -colon and uterus - just don’t generate the same buzz, attention, anxiety, awareness, and questions as do breast and ovarian cancers.

PTEN Hamartoma Tumor Syndrome

Another very rare hereditary cancer syndrome (HCS) that involves the breast and gynecologic cancers is PTEN Hamartoma Tumor Syndrome. It is also autosomal dominant in inheritance and is characterized by high cancer risks:

  • Up to 85% lifetime risk of breast cancer
  • 35% risk of thyroid cancer
  • 28% risk of uterine cancer
  • 34% risk of kidney cancer
  • 9% risk of colon cancer
  • 6% risk of melanoma

Persons with PTN also commonly have large heads, skin tags, uterine fibroids, lipomas and thyroid nodules.

Li-Fraumeni Syndrome

Li-Fraumeni syndrome is a rare cancer syndrome associated with very early onset breast cancer, brain tumors, leukemias, adrenocortical carcinomas and soft tissue sarcomas.

Hereditary Diffuse Gastric Cancer Syndrome

Hereditary Diffuse Gastric Cancer Syndrome (mutation in the CDH1 gene) is associated with lobular breast cancer and diffuse gastric cancer.

Are All Cancers Genetic?

What is important to know is that most female cancers are NOT genetic.

  • 10-15% of breast cancers are genetic
  • 25% of ovarian cancers are genetic
  • 10% of uterine and colon cancers are genetic

This accounts for 60,000 cancer diagnoses in the U.S. every year – cancers that could be caught earlier or prevented altogether.

KNOW YOUR FAMILY medical history. Any family member with any early onset cancer should raise concern. Do not just focus on the breast!

"Red flags" that may lead to hereditary cancer diagnosis are:

- Breast cancer diagnosed under age 50

- Bilateral breast cancer

- Ovarian cancer at any age

- Triple negative breast cancer

- Male breast cancer

- Metastatic prostate cancer

- Pancreatic cancer

- Colon cancer diagnosed under age 50

- Uterine cancer diagnosed under age 50

- Ashkenazi Jewish individuals with or without personal or family history ( 1 in 40 carries a BRCA mutation)

Genetic counseling has been shown to empower individuals (from movie stars to the gal next door) to make informed decisions about important medical decisions that can affect their lives and the lives of their loved ones. Women who tested negative for BRCA PRIOR to the Fall of 2013 need to return for full genetic panel testing. Many other important hereditary mutations have been identified, increasing the risk of breast and ovarian cancers, such as PALB2, CHEK2, ATM, BRIP1 and RAD51C/RAD51D.

Be Strong. Be Healthy. Be in Charge!

-Holly L. Thacker, MD and Holly J. Pederson, MD

Holly L. Thacker, MD, FACP is nationally known for her leadership in women’s health. She is the founder of the Cleveland Clinic Women’s Health Fellowship and is currently the Professor and Director of the Center for Specialized Women’s Health at Cleveland Clinic and Lerner College of Medicine at Case Western Reserve University. Her special interests are menopause and related medical problems including osteoporosis, hormone therapy, breast cancer risk assessment, menstrual disorders, female sexual dysfunction and interdisciplinary women’s health. Dr. Thacker is the Executive Director of Speaking of Women’s Health and the author of The Cleveland Clinic Guide to Menopause.

Holly J. Pederson, MD is the Director of Medical Breast Services at Cleveland Clinic and an Associate Professor of Medicine at the Cleveland Clinic Lerner College of Medicine of CWRU. Her practice focuses on breast diagnostics, breast cancer risk assessment and management of the high risk patient.

Our unique Hereditary High-Risk Clinic, run by Holly Pederson, MD, helps patients with identified mutations as well as untested family members and individuals with a strong family history. Breast cancer survivors with genetic mutations and women who have undergone risk-reducing surgery also benefit from personalized surveillance and the latest information from knowledge experts.


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