Manage Costs and Reduce Patient Harm With Consistent BRCA Testing

All cancers develop because of a mutation in a gene or multiple genes. However, most of these mutations are acquired during life and are not inherited from a parent. A few gene mutations associated with the development of certain cancers are actually inherited and are considered true hereditary cancers.

Inherited cancer-related mutations in two related genes, BRCA1 and BRCA2, can lead to a decrease in the ability to repair DNA damage and thereby can allow the development of cancer in many different sites.

A mutation in a BRCA gene is a significant risk factor for the development of breast and ovarian cancer. In comparison to the total population of patients with breast cancer, those with BRCA mutations tend to develop breast cancer much earlier in life.

Women with a BRCA mutation, particularly BRCA1, have a 20% risk of developing breast cancer before the age of 40 and a 50% risk by the age of 50.  Pooled data from a large number of studies indicate that the risk of breast cancer by age 70 is 65% for BRCA1 and 43% for BRCA2.

For ovarian cancer, various studies place the risk by age 70 at 39% for BRCA1 and 11-22% for BRCA2. In addition to breast and ovarian cancer BRCA1 is associated with an increased risk of pancreatic, uterine, prostate, melanoma, colon, cervical and occult primary cancers. BRCA2 is associated with an increased risk of cancers of the male breast, stomach and pancreas.

Given the significant risks associated with the presence of a BRCA mutation, it would be ideal if everyone were tested for this mutation. However, this is impossible given the significant expense of the testing and other factors, such as the existence of many mutations of these genes that are not significant. Widespread screening could lead to unnecessary concern and over-treatment. Therefore, it is important to determine populations in which the risk of the presence of these mutations is high and to offer genetic testing to those populations.

The affected genes are not on the sex chromosome so they can be passed on to an individual through either his/her mother or father. While the presence of a mutation in a BRCA gene is associated with an increased risk of breast or ovarian cancer, these mutations only occur in about 0.1% of the general population.  Those of Ashkenazi Jewish (Eastern European) descent have a higher incidence of approximately 2%.

BRCA mutations do not account for all of the increased risk in women with a family history of breast or ovarian cancer. It has been estimated that about 20 to 30% of women with breast cancer have at least one relative with the disease. However, only 5-10% have true “hereditary cancers,” most of which are associated with BRCA mutations.

In order to determine who should be tested for BRCA mutations, various expert groups have analyzed factors that are likely to predict the presence of a BRCA mutation in a particular family. One of those guidelines is that of the National Comprehensive Cancer Network (NCCN), which has established the following as testing criteria for BRCA analysis:

• Individual from a family with a known BRCA1/BRCA2 mutation
• Personal history of breast cancer plus one or more of the following:
  • Diagnosed at or below age 45.
  • Diagnosed at or below age 50 with one or more close blood relatives with breast cancer at or below age 50 and/or one or more close blood relatives with epithelial ovarian/fallopian tube/primary peritoneal cancer at any age. (Close relatives include first, second and third degree relatives.)
  • Two breast primaries when first breast cancer diagnosis occurred prior to age 50.
  • Diagnosed at any age, with two or more close blood relatives with breast and/or epithelial ovarian/fallopian tube/primary peritoneal cancer at any age.
  • Close male blood relative with breast cancer.
• Personal history of epithelial ovarian/fallopian tube/primary peritoneal cancer.
• For an individual of ethnicity associated with higher mutation frequency (for example, Ashkenazi Jewish), no additional family history is needed.
• Personal history of epithelial ovarian/fallopian tube/primary peritoneal cancer
• Personal history of male breast cancer
• Family History only:
  • First-or second degree blood relative meeting any of the above criteria
  • Third-degree blood relative with two or more blood relatives with breast and/or ovarian cancer (at least one close blood relative with breast cancer at or before age 50).

The NCCN also notes that individuals with early breast cancer with limited family history (fewer than two first /second degree relatives surviving beyond 45) and women diagnosed with triple negative breast cancer at or before age 40 may also be appropriate for testing given evidence that suggests an increased incidence of BRCA mutations in those populations.

Many women with breast cancer or a family history of breast cancer understandably wish to do everything possible to assess and lower their risk of breast or ovarian cancer. However, testing all these individuals would be prohibitively expensive and it is not reasonable to expect payers (either government or private) to bear such a burden. Adherence to the NCCN guidelines for the financial coverage of such genetic testing is reasonable.

An additional important consideration is the issue of appropriate genetic counseling.  Psychological and physical harm can occur if patients are tested for gene mutations such as BRCA without having access to appropriate pre- and post-testing counseling.

References:
1.     Pushkin BN, Isaacs C. Risk assessment and clinical characteristics of women with a family history of breast and/or ovarian cancer. In: Basow DS, ed. UpToDate. Waltham, MA: UpToDate; 2010.

2.     NCCN Practice Guidelines in Oncology v.2.2010 Hereditary Breast and/or Ovarian Cancer.

3.     Pushkin BN, Isaacs C, Fletcher SW. Genetic testing for breast and ovarian cancer. In: Basow DS, ed. UpToDate. Waltham, MA: UpToDate; 2010.