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    Overview

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    Harms

    Based on fair evidence from a single RCT of 4,560 women over 35 months, exemestane is associated with hot flashes and fatigue but not with fractures, osteoporosis, or cardiovascular events, compared with placebo.[5]

    Magnitude of Effect: The absolute increase in hot flashes was 8% and the absolute increase in fatigue was 2%.

    Study Design: One RCT.
    Internal Validity: Good.
    Consistency: Good.
    External Validity: Good for women who meet inclusion criteria.

    Prophylactic mastectomy

    Benefits

    Based on solid evidence, bilateral prophylactic mastectomy reduces the risk of breast cancer in women with a strong family history, and most women experience relief from anxiety about breast cancer risk. There are no studies examining breast cancer outcomes in women who undergo contralateral prophylactic mastectomy after surgery for ipsilateral breast cancer.

    Magnitude of Effect: Breast cancer risk after bilateral prophylactic mastectomy in women at high risk is reduced as much as 90%, but published study designs may have produced an overestimate.

    Study Design: Evidence obtained from case-control and cohort studies.
    Internal Validity: Good.
    Consistency: Good.
    External Validity: Good.

    Prophylactic oophorectomy or ovarian ablation

    Benefits

    Based on solid evidence, premenopausal women with BRCA gene mutations who undergo prophylactic oophorectomy have lower breast cancer incidence. Similarly, oophorectomy or ovarian ablation is associated with decreased breast cancer incidence in normal premenopausal women and in women with increased breast cancer risk resulting from thoracic irradiation.

    Magnitude of Effect: Breast cancer incidence is decreased by 50%, but published study designs may have produced an overestimate.

    Study Design: Observational, case-control, and cohort studies.
    Internal Validity: Good.
    Consistency: Good.
    External Validity: Good.

    Harms

    Based on solid evidence, castration may cause the abrupt onset of menopausal symptoms such as hot flashes, insomnia, anxiety, and depression. Long-term effects include decreased libido, vaginal dryness, and decreased bone mineral density.

    Magnitude of Effect: Nearly all women experience some sleep disturbances, mood changes, hot flashes, and bone demineralization, but the severity of these symptoms varies greatly.

    Study Design: Observational, case-control, and cohort studies.
    Internal Validity: Good.
    Consistency: Good.
    External Validity: Good.

    Bisphosphonates

    Based on fair evidence, oral or intravenous bisphosphonates decrease the risk of breast cancer.

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