BRCA mutations, breast cancer and fertility

Mutation in the breast cancer susceptibility genes (BRCA1 and 2) increases the lifetime risk for early breast and ovarian cancers. Women are commonly approached by physicians to be tested (a blood test) if they fit certain criteria that are associated with increased risk for finding these mutations. Actually there are now two software packages that allow individuals to calculate their probability of carrying a mutation and subsequently make decisions about testing. Attitudes towards testing and risk reducing procedures vary widely even among women in the same family (see for example this case study from The New York Times)

Young women carrying these mutations face several issues: Reproductive health issues

1. When should I get pregnant ? The exact impact of pregnancy and child-bearing on breast cancer risk in BRCA mutation carriers is not totally clear and may be different for BRCA 1 mutation carriers than for BRCA 2 mutation carriers in an age relater manner.

2. Are my chances for getting pregnant reduced due to these mutations ? Likely no. In spite of anecdotal suggestions that ovarian reserve (number of eggs in the ovaries) maybe diminished, this is not proven. In fact when women carrying BRCA mutations were compared to relatives who do not carrying these mutations, there were no differences in the number of deliveries and the need for fertility treatment.

3. Can I use oral contraceptive pills ? The use of OCPs reduces the risk of ovarian cancer in mutation carriers. Risk of breast cancer may be increased in BRCA1 carriers using the pill for long period of time.

Psychological issues related to risk-reducing procedures

Risk reducing bilateral salping-oophorectomy and bilateral mastectomy are commonly offered to reduce the risk of cancer in the future. Surgical removal of both ovaries and / or both breasts reduces but does not eliminate the risk (residual risk 10%). Some women report impaired body image and reduced sexual satisfaction after the procedure(s).

Future Fertility in women carrying mutations in BRCA1 and BRCA2 genes

1. Young women carrying BRCA mutations and not diagnosed with cancer are encouraged to attempt pregnancy as early as possible. If an unrelated fertility problem arises, they are encouraged to seek consultation from a reproductive endocrinologist.

2. Young women carrying BRCA mutations and diagnosed with breast can preserve their fertility through ovarian simulation and embryo or egg freezing.

3. Young women carrying BRCA mutations and elected to undergo risk-reducing removal of both ovaries should consider the following options (a or a and b) a. Ovarian stimulation followed by embryo or egg freezing and b. Ovarian tissue freezing (experimental). Since both ovaries will be removed it is reasonable to attempt to freeze ovarian tissue for future use. Future use means transplantation of ovarian tissue outside the abdomen (under the skin) followed by stimulation and egg retrieval. The tissue is then removed after pregnancy is achieved. Alternatively, if the technology permits in the future, the tissue can be cultured in the lab and eggs retrieved directly from the tissue (not successful in humans so far).

3. Young women interested in getting pregnant should be counseled to the risk of transmission of mutation to future children.

Both men and women carrying the mutation are at a significantly increased risk of cancer. It is very possible to prevent this transmission if the eggs or embryos are tested before replacement into the uterus in women undergoing in vitro fertilization – IVF Eggs are tested by polar body biopsy (this is a small cell attached to the egg and carry chromosomes representative to those of the egg). Embryos are tested by testing one cell of a 6 to 8 cell embryo. Testing has many medical and ethical dimensions and is better handled by providers specializing in these area.

Women carrying BRCA mutation can still conceive their own children and prevent the transmission of BRCA to them. With adequate support and guidance, this can be achieved even if you decided to remove both ovaries.

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