have primary ovarian insufficiency. brca mutation carriers may be more likely to give birth to girls than boys, however this observation has been attributed to ascertainment bias. if both parents are carriers of a brca mutation, then pre-implantation genetic diagnosis is sometimes used to prevent the birth of a child with brca mutations.: 82–85 inheriting two brca1 mutations (one from each parent) has never been reported and is believed to be a lethal birth defect. inheriting one brca1 mutation and one brca2 mutation has been reported occasionally; the child's risk for any given type of cancer is the higher risk of the two genes (e.g., the ovarian cancer risk from brca1 and the pancreatic cancer risk from brca2). inheriting two brca2 mutations produces fanconi anemia.: 82–85 each pregnancy in genetically typical women is associated with a significant reduction in the mother's risk of developing breast cancer after age 40. the younger the woman is at the time of her first birth, the more protection against breast cancer she receives.: 113–142 breastfeeding for more than one year protects against breast cancer.: 113–142 pregnancy also protects against ovarian cancer in genetically typical women. although some studies have produced different results, women with brca mutations are generally not expected to receive these significant protective benefits.: 113–142 current research is too limited and imprecise to permit calculation of specific risks. however, the following general trends have been identified: for women with a brca1 mutation, the woman's age when she first gives birth has no association with her risk of breast cancer. childbearing provides no protection against breast cancer, unless the woman has five or more full-term pregnancies, at which point she receives only modest protection. similar to genetically typical women, pregnancy protects against ovarian cancer in brca1 women. breastfeeding for more than one year significantly protects against breast cancer. this effect may be as high as 19% per year of breastfeeding, which is much higher than that seen among genetically typical women. the effect, if any, of long-term breastfeeding on ovarian cancer is unclear. for women with a brca2 mutation, each pregnancy is paradoxically associated with a statistically significant increase in the risk for breast cancer. unlike genetically typical women or women with brca1 mutations, breastfeeding has no effect on either cancer in women with brca2 mutations. limited and conflicting data suggest that, also unlike other women, pregnancy does not reduce ovarian cancer risk significantly in women with a brca2 mutation and might increase it. biallelic and homozygous inheritance reports of patients biallelic or homozygous for a deleterious brca allele conferring a greatly increased risk of breast cancer are rare. this is because deleterious brca alleles are lethal alleles; this condition is embryonically lethal in the majority of the cases. for live cases, inheriting both mutations lead to a grave prognosis, characterized by wilms tumors, leukemias, and early-onset brain malignancies. genetics brca mutations are inherited in a genetically dominant fashion, from either parent. the brca genes are tumour suppressor genes pictured here on their respective chromosomes. brca 1 has the cytogenetic location 17q21 or the q arm of chromosome 17 at position 21. brca 2 has the cytogenetic location 13q12.3 or the q arm of chromosome 13 at position 12.3. both genes produce proteins that help repair damaged dna, keeping the genetic material of the cell stable. a damaged brca gene in either location can lead to increased risk of cancer, particularly breast or ovarian in women. both brca genes are tumor suppressor genes that produce proteins that are used by the cell in an enzymatic pathway that makes very precise, perfectly matched repairs to dna molecules that have double-stranded breaks.: 39–50 the pathway requires proteins produced by several other genes, including chk2, fancd2 and atm. harmful mutations in any of these genes disable the gene or the protein that it produces. the cancer risk caused by brca1 and brca2 mutations are inherited in a dominant fashion even though usually only one mutated allele is directly inherited. this is because people with the mutation are likely to acquire a second mutation, leading to dominant expression of the cancer. a mutated brca gene can be inherited from either parent. because they are inherited from the parents, they are classified as hereditary or germline mutations rather than acquired or somatic mutations. cancer caused by a mutated gene inherited from an individual's parents is a hereditary cancer rather than a sporadic cancer. because humans have a diploid genome, each cell has two copies of the gene (one from each biological parent). typically only one copy contains a disabling, inherited mutation, so the affected person is heterozygous for the mutation. if the functional copy is harmed, however, then the cell is forced to use alternate dna repair mechanisms, which are more error-prone. the loss of the functional copy is called loss of heterozygosity (loh). any resulting errors in dna repair may result in cell death or a cancerous transformation of the cell.: 39–50 there are many variations in brca genes, and not all changes confer the same risks. : 39–50 some variants are harmless; others are known to be very harmful. some single nucleotide polymorphisms may confer only a small risk, or may only confer risk in the presence of other mutations or under certain circumstances. in other cases, whether the variant is harmful is unknown. variants are classified as follows:: 39–50 : 109 deleterious mutation: the change is proven to cause significant risks. often, these are frameshift mutations that prevent the cell from producing more than the first part of the necessary protein. suspected deleterious: while nothing is proven, the variation is currently believed to be harmful. variant of uncertain significance (vus): whether the change has any effect is uncertain. this is a common test result, and most variations began in this category. as more evidence is acquired, these are re-classified. variant, favor polymorphism: while nothing is proven, the variation is currently believed to be harmless. benign polymorphism: the change is classified as harmless. these may be reported as "no mutation". deleterious mutations have high, but not complete, genetic penetrance, which means that people with the mutation have a high risk of developing disease as a result, but that some people will not develop cancer despite carrying a harmful mutation. diagnosis genetic counseling is recommended in women whose personal or family health history suggests a greater than average likelihood of a mutation. the purpose of genetic counseling is to educate the person about the likelihood of a positive result, the risks and benefits of being tested, the limitations of the tests, the practical meaning of the results, and the risk-reducing actions that could be taken if the results are positive. they are also trained to support people through any emotional reactions and to be a neutral person who helps the client make his or her own decision in an informed consent model, without pushing the client to do what the counselor might do. because the knowledge of a mutation can produce substantial anxiety, some people choose not to be tested or to postpone testing until a later date.: 51–74 relative indications for testing for a mutation in brca1 or brca2 for newly diagnosed or family members include a family history among 1st (fdr), 2nd (sdr), or 3rd(tdr) degree relatives usually on the same side of the family but not limited: a known mutation (brca1 or brca2) in a cancer susceptibility gene within the family women affected by any breast cancer diagnosed under the age of 30 women affected by triple negative breast cancer (tnbc) (estrogen receptor negative, progesterone receptor negative, and her2/neu negative) under the age of 50 two relatives (fdr/sdr) diagnosed under the age of 45 three relatives (fdr/sdr) diagnosed with average age of 50 or less four relatives at any ages ovarian cancer with either an additional diagnosed relative or a relative with male breast cancer a single family member with both breast and ovarian cancer male breast cancer pancreatic cancer with breast or ovarian cancer in the same individual or on the same side of the family ashkenazi jewish or polish ancestry with one fdr family member affected by breast or ovarian cancer at any age testing young children is considered medically unethical because the test results would not change the way the child's health is cared for.: 82–85 test procedure two types of tests are available.: 51–74 both commonly use a blood sample, although testing can be done on saliva. the quickest, simplest, and lowest cost test uses positive test results from a blood relative and checks only for the single mutation that is known to be present in the family. if no relative has previously disclosed positive test results, then a full test that checks the entire sequence of both brca1 and brca2 can be performed. in some cases, because of the founder effect, jewish ethnicity can be used to narrow the testing to quickly check for the three most common mutations seen among ashkenazi jews.: 51–74 testing is commonly covered by health insurance and public healthcare programs for people at high risk for having a mutation, and not covered for people at low risk.: 51–74 the purpose of limiting the testing to high-risk people is to increase the likelihood that the person will receive a meaningful, actionable result from the test, rather than identifying a variant of unknown significance (vus). in canada, people who demonstrate their high-risk status by meeting specified guidelines are referred initially to a specialized program for hereditary cancers, and, if they choose to be tested, the cost of the test is fully covered. in the us in 2010, single-site testing had a retail cost of us$400 to $500, and full-length analysis cost about $3,000 per gene, and the costs were commonly covered by private health insurance for people deemed to be at high risk. the test is ordered by a physician, usually an oncologist, and the results are always returned to the physician, rather than directly to the patient. how quickly results are returned depends on the test—single-site analysis requires less lab time—and on the infrastructure in place. in the us, test results are commonly returned within one to several weeks; in canada, patients commonly wait for eight to ten months for test results.: 51–74 test interpretation a positive test result for a known deleterious mutation is proof of a predisposition, although it does not guarantee that the person will develop any type of cancer. a negative test result, if a specific mutation is known to be present in the family, shows that the person does not have a brca-related predisposition for cancer, although it does not guarantee that the person will not develop a non-hereditary case of cancer. by itself, a negative test result does not mean that the patient has no hereditary predisposition for breast or ovarian cancer. the family may have some other genetic predisposition for cancer, involving some other gene.: 89–111 cancer prevention a variety of screening options and interventions are available to manage brca-related cancer risks. screenings are adjusted to individual and familial risk factors. as these screening methods do not prevent cancer, but merely attempt to catch it early, numerous methods of prevention are sometimes practiced, with varying results.: 175–207 screening an intensive cancer screening regimen is usually advised for women with deleterious or suspected deleterious brca mutations in order to detect new cancers as early as possible. a typical recommendation includes frequent breast cancer screening as well as tests to detect ovarian cancer.: 175–207 breast imaging studies usually include a breast mri (magnetic resonance imaging) once a year, beginning between ages 20 and 30, depending on the age at which any relatives were diagnosed with breast cancer. mammograms are typically used only at advanced age as there is reason to believe that brca carriers are more susceptible to breast cancer induction by x-ray damage than general population. alternatives include breast ultrasonography, ct scans, pet scans, scintimammography, elastography, thermography, ductal lavage, and experimental screening protocols, some of which hope to identify biomarkers for breast cancer (molecules that appear in the blood when breast cancer begins).: 175–207 ovarian cancer screening usually involves ultrasonography of the pelvic region, typically twice a year.: 175–207 women may also use a blood test for ca-125 and clinical pelvic exams. the blood test has relatively