Pathology Associates Of Lexington, P.A.

Genetic testing in breast cancer

Genetic testing is expensive and gives results which express probabilities (usually not quite the specific prediction for your personal case). The decision to test and the lab to perform the testing are significant decisions and should rest on the advice of a physician with a great deal of experience in treating patients with breast cancer. A negative test does not mean that you have no risk, low risk, or high risk. A positive test does not mean that you will get breast cancer. But a negative test might give a type of information that would allow staving off radical prophylactic surgery (read the riveting story of having the discover of this test press it prematurely into use for a specific clinical situation¹).

RISK: USA background, general breast cancer lifetime risk is 1 in 8 (13% =130 out of every 1000 women)........and 7 in 8 don't get it.

INHERITED/FAMILIAL: Some 20% of women who get breast cancer have a positive family history of breast cancer (26 out of those every 1000 women). AND 1/4th of those (6 out of every 1000 women) get their cancer by way of passing on a gene...BRCA1 or BRCA2...with an autosomal dominant mode of inheritance (so, the other 124 per 1000 breast cancers seem to arise by way of acquired, sporadic, breast cell mutations in their own generation).

if your mother or sister got breast cancer after menopause, you have 2-3 times the average lifetime risk
if your mother or sister got breast cancer before menopause, you have 9 times the average lifetime risk

As of Jan. 2002, abnormalities in 6 genes & gene regions are associated with increased breast cancer risk:

BRCA1: more likely carried by Ashkenazy Jewish women; present @ lower stage and earlier age (43 years); tumors high grade & high proliferation rate; medullary & atypical medullary cancers often this group; any ovarian cancers usually present @ younger age and as serous variety
BRCA2: also more likely carried by Ashkenazy Jewish women
TP53
Cowden
AR (androgen receptor gene)
AT (ataxia telangiectasia gene)

of women WITH breast cancer, 1 in 10 is positive for a genetic mutation in BRCA1 or BRCA2
persons WITH a mutation in BRCA1 or BRCA2 have a 50/50 chance of passing the mutation to the next generation
within the cohort of women in the risk studies of the BRCA mutations, it appears that there is an 82-85% risk that the ones with BRCA1 mutation will get breast cancer by age 70; 18% do not get breast cancer (and no one can predict which). When a patient has invasive or non-invasive breast cancer and siblings/parent-aunts with breast or ovarian cancer, genetic testing is indicated and, if positive, prophylactic bilateral mastectomies with bilateral removal of ovaries may be indicated if gene test positive [LMC-04-1213].
within the cohort of women in the risk studies of the BRCA mutations, it appears that there is a 60-65% risk that the ones with BRCA2 mutation will get breast cancer by age 70 (35-40% do not get breast cancer (and no one can predict which)...and 83-87% get breast cancer by age 80
USA background, general ovarian cancer lifetime risk is 1 in 100 (1%; 1 out of every 100 women) and 99 out of every 100 don't get it
within the cohort of women in the risk studies of the BRCA mutations, it appears that there is an 44-63% risk that the ones with BRCA1 or BRCA2 mutation will get ovarian cancer by age 70; 56% do not get ovarian cancer (and no one can predict which)
prohylactic bilateral salpingoophorectomies may be performed in these cases and require an "intense protocol" type of microscopic exam to find occult ovarian cancer AS WELL AS fallopian tube cancer and dysplasia [L10-10970].

Take-home Points:
getting your correct family history by age 30 is of life-saving importance; and, if positive for deadly cancers, see an oncologist about an optimal surveillance plan for you.
testing for the BRCA1 & 2 is currently available; but, a positive test does not mean that you will get cancer & a negative test does not mean that you will not.
if you are positive for BRCA1 or 2:
1. FOLLOW UP: this might indicate risk odds so high that you take great care to have very careful and optimized surveillance; or,
2. SURGERY: this might indicate risk odds so high that you decide to chose preventive surgery & have both breasts removed (but microscopic breast tissue may not all be removed...so this surgery is not an absolute guarantee of safety from breast cancer) and maybe both ovaries, also.

References:

Collins, Francis S. [an M. D. & PhD final "head" of the human genome project], The Language of God: A Scientist Presents Evidence For Belief (see pages 236-239), 294 pages, 2006.
JAMA Patient Page, 1 June 2011 HERE.

(posted January 2002; partial update 19 February 2004; latest addn 6 June 2011)