For BRCA families

[AlaskaAngel]

BRCA's - see article posted at end of my comments.

On a related matter --

I don't know if there is a way to separate out the causes and effects, but considering how slow medical providers and insurers are to move away from mammograms for people with dense breast tissue, the question of whether those with prior bc history genuinely have an increased risk of further cancers in the breasts or whether they just have a more consistent track record for having mammograms than those who haven't had bc remains very real to ME.

Also, if HER2+++ bc is happening generally in a younger age group, and if its growth is faster than other bc, might that be an indicator that it has a relationship to prior x-rays and mammograms that is similar to that of the BRCA's? These are just questions -- that I have to ask.

BRCA ARTICLE FOLLOWS


Chest X-ray increases cancer risk in BRCA1/2 carriers

Reuters Health
Posting Date: August 2, 2006

Last Updated: 2006-08-02 17:13:05 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Researchers with the International BRCA1/2 Carrier Cohort Study (IBCCS) report that exposure to chest X-rays has a "relatively large effect" on breast cancer risk in mutation carriers.

Studies have shown that young girls who receive repeated X-rays for assessment of scoliosis have an increased risk of breast cancer. Dr. David Goldgar of Case Western Reserve University in Cleveland, Ohio, and colleagues retrospectively evaluated 1601 women who were either BRCA1 or BRCA2 carriers and were exposed to routine, occasional and conventional chest X-rays for screening or diagnosis to assess risk of breast cancer.

These women already have a high risk of breast cancer without the possible risk increase conveyed by chest X-rays.

The IBCCS members found that any reported exposure to chest X-rays was associated with a hazard ratio (HR) of 1.54. Women 40 years old or younger had an even higher risk of breast cancer after chest X-ray exposure with an HR of 1.97. Women born after 1949 had an HR of 2.56. BRCA1/2 carriers exposed to chest X-rays before age 20 had the highest risk, with an HR of 4.64.

The IBCCS researchers report their latest findings in the July 20th issue of the Journal of Clinical Oncology. The investigators write that "diagnostic ionizing radiation exposure from chest X-rays may be associated with significant breast cancer risk among women" with the BRCA1 or BRCA2 germline mutation.

A significantly increased risk of breast cancer in BRCA1/2 carriers occurred at radiation doses considerably lower than levels associated with increased risk in other populations (largely noncarriers).

The average dose was typically low, Dr. Goldgar's group notes. The total dose received by women who underwent a large number of chest X-rays was "unlikely to exceed 10 mGy to 20 mGy."

The IBCCS investigators recommend a careful risk-benefit analysis of chest X-rays in young BRCA1/2 carriers, but they caution that the results still need to be confirmed and that these findings could be influenced by recall bias.

J Clin Oncol 2006;24:3361-3366.

[Christine MH-UK]

I wondered about this because I had a chest x-ray in my 20s to get a student visa for a country (it was a check for TB, even though I was in an area that didn't have a TB problem).

Recently, I ran across the study below which compared the traits of premenopausal breast cancers associated with Chernobyl and those in Western New York state. From this, it sounds like her2 neu negative cancers are more like those caused by radiation.

1: Br J Cancer. 2005 Sep 19;93(6):699-708.

Array comparative genomic hybridisation (aCGH) analysis of premenopausal breast cancers from a nuclear fallout area and matched cases from Western New York.

Varma G, Varma R, Huang H, Pryshchepava A, Groth J, Fleming D, Nowak NJ, McQuaid
D, Conroy J, Mahoney M, Moysich K, Falkner KL, Geradts J.

Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA.

High-resolution array comparative genomic hybridisation (aCGH) analysis of DNA copy number aberrations (CNAs) was performed on breast carcinomas in
premenopausal women from Western New York (WNY) and from Gomel, Belarus, an area exposed to fallout from the 1986 Chernobyl nuclear accident. Genomic DNA was isolated from 47 frozen tumour specimens from 42 patients and hybridised to arrays spotted with more than 3000 BAC clones. In all, 20 samples were from WNY and 27 were from Belarus. In total, 34 samples were primary tumours and 13 were lymph node metastases, including five matched pairs from Gomel. The average number of total CNAs per sample was 76 (range 35-134). We identified 152 CNAs (92 gains and 60 losses) occurring in more than 10% of the samples. The most common amplifications included gains at 8q13.2 (49%), at 1p21.1 (36%), and at 8q24.21 (36%). The most common deletions were at 1p36.22 (26%), at 17p13.2 (26%), and at 8p23.3 (23%). Belarussian tumours had more amplifications and fewer deletions than WNY breast cancers. HER2/neu negativity and younger age
were also associated with a higher number of gains and fewer losses. In the five paired samples, we observed more discordant than concordant DNA changes.
Unsupervised hierarchical cluster analysis revealed two distinct groups of
tumours: one comprised predominantly of Belarussian carcinomas and the other
largely consisting of WNY cases. In total, 50 CNAs occurred significantly more
commonly in one cohort vs the other, and these included some candidate signature amplifications in the breast cancers in women exposed to significant radiation.
In conclusion, our high-density aCGH study has revealed a large number of
genetic aberrations in individual premenopausal breast cancer specimens, some of which had not been reported before. We identified a distinct CNA profile for carcinomas from a nuclear fallout area, suggesting a possible molecular fingerprint of radiation-associated breast cancer.

PMID: 16222315 [PubMed - indexed for MEDLINE]