1. The US preventive service taskforce (USPSTF) just released their guidelines for BRCA testing (see http://www.uspreventiveservicestaskforce.org/uspstf12/brcatest/brcatestfinalrs.htm). in brief, they suggest:
–estimated prevalence of BRCA1 or 2 is 0.2% to 0.3% (ie, 1 in 300-500 women) in the general population of women, 6.0% in women with cancer onset before age 40 years, and 2.1% in the general population of Ashkenazi Jewish women. In a meta-analysis of studies in which recruitment was based on family history of breast or ovarian cancer, BRCA1 mutation prevalence was 13.6%, BRCA2 mutation prevalence was 7.9%, and prevalence of either mutation was 19.8%.
–A woman’s risk for breast cancer increases to 45% to 65% by age 70 years if there are clinically significant mutations in either BRCA gene. Mutations in the BRCA1 gene increase ovarian cancer risk to 39% by age 70 years, and BRCA2 mutations increase ovarian cancer risk to 10% to 17% by age 70 years.
–USPSTF recommends that primary care providers screen women who have family members with breast, ovarian, tubal, or peritoneal cancer with 1 of several screening tools designed to identify a family history that may be associated with an increased risk for potentially harmful mutations in breast cancer susceptibility genes (BRCA1 or BRCA2). Women with positive screening results should receive genetic counseling and, if indicated after counseling, BRCA testing. (B recommendation). one of the simplest tools is below (they list several in their guidelines, though note that the Gail model is not designed for BRCA testing/risk assessment):
| Did any of your first-degree relatives have breast or ovarian cancer? |
| Did any of your relatives have bilateral breast cancer? |
| Did any man in your family have breast cancer? |
| Did any woman in your family have breast and ovarian cancer? |
| Did any woman in your family have breast cancer before age 50 y? |
| Do you have 2 or more relatives with breast and/orovarian cancer? |
| Do you have 2 or more relatives with breast and/or bowel cancer? |
One positive response initiates referral.
–The USPSTF recommends against routine genetic counseling or BRCA testing for women whose family history is not associated with an increased risk for potentially harmful mutations in the BRCA1or BRCA2 genes. (D recommendation)
2. USPSTF also recently came out with recommendations about medication use to reduce risk of development of breast cancer in high risk women (see http://www.uspreventiveservicestaskforce.org/uspstf13/breastcanmeds/breastcanmedsrs.htm). here are there conclusions:
— adequate evidence exists that treatment with tamoxifen or raloxifene can significantly reduce the relative risk (RR) for invasive ER-positive breast cancer in postmenopausal women who are at increased risk for breast cancer
–tamoxifen and raloxifene, in a systematic review, reduced the incidence of invasive breast cancer by 7 to 9 events per 1000 women over 5 years; tamoxifen reduced breast cancer incidence more than raloxifene. Tamoxifen also reduces the incidence of invasive breast cancer in premenopausal women who are at increased risk.
–women with an estimated 5-year risk of 3% or greater (basically using the Gail model) should be considered for treatment. see their figures 1-4, which display benefit-risk of using tamoxifen vs raloxifene in 4 subgroups at different risk levels — nonhispanic white women with and without uterus, and similarly for black women.
–the benefits of tamoxifen and raloxifene for breast cancer risk reduction are no greater than small in women who are not at increased risk for the disease. (a bit convoluted: basically, not use meds if woman not at increased risk)
–In addition to breast cancer risk reduction, the USPSTF found adequate evidence that tamoxifen and raloxifene reduce the risk for nonvertebral or vertebral fractures, respectively, in postmenopausal women.
–BUT, tamoxifen and raloxifene increase risk for venous thromboembolic events (VTEs) by 4 to 7 events per 1000 women over 5 years and that tamoxifen increases risk more than raloxifene. the potential harms from thromboembolic events are small to moderate, with increased potential for harms in older women.
— tamoxifen but not raloxifene increases risk for endometrial cancer (4 more cases per 1000 women — and i might add that these are typically more aggressive cancers). Potential harms from tamoxifen-related endometrial cancer are small to moderate and depend on hysterectomy status and age. The potential risks for tamoxifen-related harms are higher in women older than 50 years and in women with a uterus. Tamoxifen may also increase the incidence of cataracts.
–Vasomotor symptoms (hot flashes) are a common adverse effect of both medications that is not typically classified as serious, but these symptoms may affect a patient’s quality of life and willingness to use or adhere to these medications.
–so, their conclusions are that there is moderate certainty that there is a moderate net benefit from use of tamoxifen and raloxifene to reduce the incidence of invasive breast cancer in women who are at increased risk for the disease, and with moderate certainty that the potential harms of tamoxifen and raloxifene outweigh the potential benefits for breast cancer risk reduction in women who are not at increased risk for the disease.
3. an editorial in the NY times this week by H. Gilbert Welch (http://www.nytimes.com/2013/12/30/opinion/breast-cancer-screenings-what-we-still-dont-know.html?(inl=todaysheadlines&emc=edit_th_20131230&_r=0) highlighted several issues about mammography, with the following statistics. for one thousand 50yo women screened yearly for 10 years (with range from low to high estimates, based on studies):
–490-670 will have a false positive test
–3-14 will be overdiagnosed (ie, diagnosed with cancer, getting therapy, but having a “cancer” which would never have caused a problem: ie, leading to overtreatment)
–but only 0.3-3.2 will avoid a breast cancer death
so,
–mammography is a pretty rotten screening test, with high numbers of false positives and overtreatment, and small numbers of “lives saved”. note that the estimates by Welch are for annual mammograms for ten years in women over age 50, and not annual from age 50-75 as typically recommended, or even 40-75 as is often done.
–one very intriguing comment by Welch is that perhaps much of the apparent benefit of screening may be subsumed by the improvement in treatments (ie, does screening continue to be beneficial if treatment is much more effective and better tolerated than before? perhaps screening really adds nothing now since the new and earlier treatments are more effective? remember that the above benefits for treatment in Gilbert’s article are based on old studies prior to current therapies). i would add here that more aggressive screening of very high risk patients (eg BRCA’s, as above) and other high risk as determined by Gail model (using prophylactic tamoxifen/raloxifene as above) would also likely undercut the benefit of mammography further.
–BUT, mammography is what we have now, and above considerations (which i think are important) are not adequately studied to result in a shift in current screening recommendations. the only change i have made in my practice as a result of recent studies is to offer women at age 50 the option of screening every 2 years, which (per the annals of intl medicine article i sent out several months ago) is associated with fewer false positives and little impact on true positives. i also do screening mammograms on women from 40-50 if they so desire, though i indicate that screening is quite controversial (similar to my approach on PSA screening — shared decision-making).
–and, unfortunately, none of these guidelines focus on the most important issue: breast cancer results from an accumulation of pathologic mutations over decades, and that the likelihood is quite high (in my opinion) that industrial and environmental toxins play an important role here. given the huge numbers of untested toxins currently used, and given the large number introduced into industry yearly that are never tested for potential carcinogenesis, probably the single most important preventative strategy is to focus on widespread testing of chemicals used, which often make it into the environment or the food chain — a proposal which is consistently rebuffed by industry and their governmental lobbies.
geoff