© 2017, GENASSIST, Inc.

By Keith S. Wexler, MBA, Maternal Fetal Medicine, Prenatal Diagnosis and Biotech/Life Sciences Consultant, GENASSIST, Inc.

Paul Wexler, M.D., F.A.C.O.G., Medical Director, GENASSIST, Inc.

Clinical Professor, Department of OB/GYN, University of Colorado Health Sciences Center

Clinical Professor, Division of Genetics/Dept. of Pediatrics, Univ. of Colorado/The Children’s Hospital

 Overview:

Breast Cancer: Is one of the most common cancers in women with an approximate lifetime risk for a non-Hispanic female of 1:8 (12.5%). The risk is progressively lower in African-American, American Indian, Asian and/or Pacific Islander and Hispanic-Latino females. However, the mortality rate is higher in African American females.

There are many factors implicated in increasing the risk for breast cancer.  These include:

  • Gender (higher in females)
  • Aging (2 out of 3 cancers are in patients over age 55)
  • Genetic factors
  • History of prior breast cancer
  • Race
  • Dense breast tissue (1.2 to 2 times increased risk)
  • Early onset of menses (less than 12 years of age)
  • Late menopause (after 55 years of age)
  • Breast conditions (slightly increased with cysts, cystic mastitis, hyperplasia, adenosis, fat necrosis, metaplasia, some calcifications, some benign tumors).
  • Atypical hyperplasia
  • DES (diethylstilbesterol)
  • Chest irradiation especially in adolescence
  • Later childbearing

Other factors having lesser or uncertain impact on risk: 

  • Birth control pills – slightly increased risk
  • Hormone Replacement Therapy (HRT) especially synthetic progestin
  • Alcohol
  • No breast feeding
  • Overweight
  • Tobacco
  • Night work

Factors probably not associated with increased risks: 

  • Bras
  • Antiperspirants
  • Miscarriage
  • Breast implants

 Breast Cancer Screening Tests: 

  • Monthly breast self-examination in a menstruating female shortly after a menses or at least 3-4 times yearly. Monthly self -breast examination in postmenopausal women or a woman post-hysterectomy or at least 3-4 times yearly.
  • Annual mammogram beginning at age 40 years or 10 years earlier than the earliest breast cancer in a first or second degree relative or male first or second degree relative with breast cancer.
  • Breast Mammography:   May detect breast cancers that are smaller than can be diagnosed by self-examination or examination by a clinician and may detect cancers 1-5 years earlier than might otherwise be diagnosed. It can also help distinguish benign cysts or benign tumors. X-ray images of the breast are captured on film.
  • Digital Mammography:   Is the capturing of X-ray pictures from a mammogram on a computer which can then be enhanced and enlarged to make interpretation and diagnosis more accurate.
  • Breast Ultrasound: Is often used in conjunction with a mammogram when a mass or lump is felt by a patient or clinician or found on a mammogram. It can help distinguish cysts from solid tumors and may be used to assist performing a biopsy or removal of fluid from a cyst.
  • Breast MRI: For women at high risk for breast cancer. Generally it is recommended to be used in addition to rather than instead of mammography. It may detect up to 10 percent more breast cancer than mammography but may miss other breast cancer easily detected with mammography.
  • High Risk Patients: May begin MRI at age 30 and includes patients with a known BRCA1 or BRCA2 mutation or other mutation associated with an increased risk for breast cancer. Patients at greater than a
  • 20 percent risk of developing breast cancer. Patients with a syndrome known to increase the risk for breast cancer or a first degree relative with one of these syndromes known to increase risk e.g. Cowden Syndrome/Bannayan-Riley-Ruvalcaba.
  • 3D Mammography (3D Breast Tomosynthesis): Multiple low dose images at different angles of the breast are acquired and produces multiple thin slices of the breast to provide a 3D reconstruction of the breast. It currently is the best routine imaging method for studying the breast but may not be completely reimbursed by insurance.

Breast Cancer Risk Reduction in High Risk Patients: It has been shown that the use of Tamoxifen (20 mg per day for 5 years) will lower the risk for development of breast cancer in women at a risk of 1.7 times the risk of the general population or greater. However, the drug will cause hot flashes and has an increased risk for the development of blood clots, uterine (endometrial) cancer and cataracts.

One recent report suggested a possible increase in the risk of developing a rare, but more aggressive, tumor of the uterus (sarcoma). Evista (raloxifene – 60 mg per day for 5 years) appears to confer a similar benefit to Tamoxifen. Evista is used to lower the risk for the development of osteoporosis.

However, it has an increased risk for causing hot flashes and blood clotting events. It does not appear to increase the risk for the development of cancer of the uterus.

Aromatase Inhibitors (exemestane or anastrozole – 25 mg per day for 5 years) lowers the amount of circulating estrogen in postmenopausal women.

It may accelerate bone loss and cause hot flashes but a benefit of lowering the risk of breast cancer possibly by up to 70 percent probably outweighs the risk.All of these drugs are for estrogen receptor positive breast cancer prevention.

Analysis:  In patients found to be at high risk for breast and/or ovarian cancer and/or women who test positive for a mutation in the BRCA1 or BRCA2 genes or possibly other mutations known to increase the risk for breast cancer, bilateral simple mastectomy with reconstruction will lower the risk for breast cancer by approximately 90-95%.

Bilateral oophorectomy will also lower the risk for ovarian cancer by 90-95% in patients with mutations in BRCA1 or BRCA2.

The availability of genetic screening panels for diagnosis and prediction of risk are continuing to expand.

Recently three companies have begun to offer expanded panels looking at 7, 27, 28, 31 and 80 specific gene mutations implicated in various cancers including breast, ovarian, colorectal, uterine, stomach, prostate, melanoma and pancreas.

Most of these tests include the well-known screening for the BRCA1 and BRCA2 genes which can increase the likelihood of the development of breast and ovarian cancer and several other cancers.

Currently at least 13 genes increasing breast cancer susceptibility have been identified.There are current limitations to those panels. Also, insurance companies limit access because: 

  • It may not be considered “standard of care”
  • Only patients identified as “high risk” may be considered candidates for testing
  • Tests are expensive and will NOT identify all patients at increased risk
  • Many patients will be unable or unwilling to pay their patient share (pay high deductible for a single test)
  • Patients are unsure of how to be monitored if a gene known or suspected to increase their cancer risk is identified.

The introduction of multiple panels for known hereditary cancer susceptibility or cancers suspected or not known to be “familial” will make panel selection for any individual patient a challenge.

Use of multiple panels will probably not be financially feasible for most patients nor even recommended. Therefore, the decision as to what panels to order, when to order them and what to do with the information when a positive result for increased susceptibility returns will remain problematic.