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Management of an Inherited Predisposition to Breast Cancer | NEJM July 23, 2007

Posted by ramunas in BRCA, breast cancer, cancer genetics, familial cancer, genetic testing, hereditary cancer.

There have been recently a nice review about management of inherited predisposition to breast cancer published in NEJM. It is also possible to listen to this article via audio podcast stream, a new service offered by NEJM as a beta version (and don’t forget to vote).

There are several quotes which seems to be important for me (from a point of good summary):

Recent estimates of breast-cancer risk by the age of 80 years are 90% for carriers of the BRCA1 mutation and 40% for carriers of the BRCA2 mutation, with corresponding risks of ovarian cancer of 24% and 8%, respectively; annual risks vary according to age:

(My note:  to analyze properly the graph above, you should remember, that lifetime risk for a female breast cancer in a western population is about 10-12% and for ovarian – about 2,5%. [Ref.])

Although imperfect, annual mammography is recommended for women with BRCA mutations beginning between the ages of 25 and 30 years, when breast-cancer risk begins to increase.10,37 For women without documented BRCA mutations who have a substantial familial risk of breast cancer, screening is suggested to begin at an age that is 5 to 10 years earlier than the youngest age at diagnosis in the family. The recent Digital Mammographic Imaging Screening Trial (DMIST) reported that digital mammography may be more accurate than mammography without computer-aided detection in younger women or in those with dense breasts.

(my comment: mammography before the age 30 is not recommended according UK NICE guidelines and I support this view, because a breast tissue is too dense.)

MRI should be considered as a complement to mammography, rather than as a replacement…The positive predictive value is expected to be lower in lower-risk populations, and MRI screening is likely to be most cost-effective for mutation carriers (as opposed to women at lower risk),43 particularly for BRCA1 carriers and for the subgroup of BRCA2 carriers with dense breasts.44

Ultrasonography did identify a significant number of mammographically occult tumors. Of the 83 cancers in these series, only 32 (39%) would have been identified by mammography alone, whereas 45 (54%) would have been detected by a combination of mammography and ultrasonography. This finding suggests that ultrasonography may add benefit beyond mammography alone in women with a hereditary risk but provides little incremental benefit in women undergoing screening with MRI.

Screening for other BRCA-associated cancers (e.g., ovarian, prostate, male breast, and pancreatic cancers) is often recommended even though there is no clear proof of benefit.

Risk-reducing salpingo-oophorectomy (RRSO) is an important preventive intervention in BRCA mutation carriers. Although this surgery has not been evaluated in randomized trials, retrospective and prospective cohort studies indicate a reduction in the risk of BRCA-associated gynecologic cancer of 80 to 96%57,58,59 and a reduction in the risk of breast cancer of approximately 50%, most likely through the induction of premature menopause.58,59,60

Risk-reducing mastectomy (RRM) reduces the risk of breast cancer by at least 90% in mutation carriers… RRSO and RRM do not entirely prevent the risk of subsequent breast or ovarian cancer. The residual risk of primary peritoneal cancer after RRSO has been reported to be 0.2% annually.57 The absolute risk after RRM has not been clearly defined.

No randomized, controlled trials of screening methods or prophylactic interventions have been conducted specifically in mutation carriers; guidelines are based largely on expert opinion and on observational studies and trials involving women at high risk for cancer… Randomized, controlled trials of surgical interventions to prove mortality benefits are not likely to be feasible.

Data are also needed regarding the optimal duration and time to initiate hormonal chemoprevention in young women identified as having a hereditary risk for breast cancer. Finally, the potential role of preimplantation genetic diagnosis in women who carry BRCA mutations warrants consideration; data are needed regarding the safety of hormonal treatments that are used to induce ovulation in these women.

Ultrasonography and breast examination may increase detection rates slightly but at a cost of more false positive results and additional evaluations. Preventive mastectomy and salpingo-oophorectomy for BRCA mutation carriers are options that should be discussed with women who are at increased risk. Oophorectomy is performed after childbearing, since the greatest increase in the risk of ovarian cancer occurs later than that of breast cancer in BRCA mutation carriers.



1. Steven Murphy MD - July 24, 2007

This is an excellent article and I am using it to help teach residents about management of Hereditary Breast and Ovarian cancers. Thanks for posting it.

2. drcancer - August 27, 2010

Nice Blog Great Informatin And Those Info Are very Useful Cancer

3. drcancer - December 9, 2010

great i just say this is a awesom blog Make Us Healthy

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