Figure 9 summarizes the evidence for key questions 4 and 5. It shows the analytic framework starting at genetic testing with one arrow leading to a box that describes three possible results of testing: BRCA mutation detected, variant of uncertain significance, or uninformative negative. An arrow connects these possible genetic test results to a box that describes the clinical health outcomes of reduced incidence of BRCA-related cancer and reduced cancer-specific and all-cause mortality via the use of interventions, which are the subject of key questions 4 and 5. A second arrow from genetic testing leads to a fourth possible result of testing: true negative. There is no further action beyond that result. Below and to the left of the analytic framework is a table labeled “KQ 4: Benefits of Interventions.” Below and to the right of the analytic framework is a table labeled “KQ 5: Adverse Effects of Interventions.”

Figure 9Summary of Key Questions 4 and 5

Abbreviations: CA-125 = cancer antigen-125; MRI = magnetic resonance imaging; RRM = risk-reducing mastectomy; RRSO = risk-reducing salpingo-oophorectomy; TVUS = transvaginal ultrasound.

KQ 4. Benefits of Interventions
InterventionRisk Reduction
Intensive ScreeningNo effectiveness studies
Risk-Reducing Medications
Invasive breast cancer30%−68%*
Ovarian cancerNo significant reduction
MortalityNo significant reduction
Risk-Reducing Surgery
Breast cancerRRM: 85%−100%; RRSO:37%−100%
Ovarian cancerRRSO:S9%−100%
MortalityRRM: 81%−100%breastcancer; RRSO: 55%−100% all-cause
KQ 5. Adverse Effects of Interventions
InterventionRates
Intensive Screening (per episode or year)
False-positive4.6%−15% mammogram; 8.2%−14% MRI;3.4%TVUS
Recall3.9% mammogram; 11%MRI
Unneeded biopsy27%−28% mammogram; 25%−43% MRI; 100%TVUS; 67%CA−125
Risk-Reducing Medication (over 5 years)
Venous thrombosis0.4%−0.7%
Endometrial cancerTamoxifen: 0.4%
Risk-Reducing Surgery
ComplicationsRRM: 3%−59%; RRSO: no studies
SymptomsRRM: 64%−87%; RRSO: no studies
Quality of lifeRM: decrease anxiety; sexual
RRSO: decrease sexual
*

Risk reduction for all women; analysis by family history was similar.

Includes studies of oophorectomy alone.

Includes some women with symptoms.

From: 4, DISCUSSION

Cover of Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer
Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer: Systematic Review to Update the U.S. Preventive Services Task Force Recommendation [Internet].
Evidence Syntheses, No. 101.
Nelson HD, Fu R, Goddard K, et al.

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