Pricing of genetic tests

Young first-time mothers decrease the risk of breast cancer – here’s why:

One single full-term pregnancy in women in their 20’s decreases the risk for estrogen receptor-positive postmenopausal breast cancer, which is the most common form of the disease. However, BRCA1 and BRCA2 mutation carriers do not experience a similar reduction in the risk for breast cancer even with a full term pregnancy in their mid 20’s, as do women in the general population.

An international scientific collaborative led by the Harvard Stem Cell Institute’s principal faculty member Kornelia Polyak, and Saraswati Sukumar, a professor at Johns Hopkins University School of Medicine, has discovered why.

Breast Cancer Risk Reduction- The Impact of First Pregnancy

Age at first live birth # of affected relatives

0

1

2 or more

20 or younger

1

2.6

6.8

20-24

1.2

2.7

5.8

25-29 or no child

1.5

2.8

4.9

30 or older

1.9

2.8

4.2

* Adapted from Table 1, Gail MH, Brinton LA, Byar DP, Corle DK, Green SB, Shairer C, Mulvihill JJ: Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. J Natl Cancer Inst 81(24):1879-86, 1989.

Breast Cancer Prevention Rather Than The Cure Should Be The Focus

The research, a collaboration between clinicians at cancer centers, genomics experts and bioinformaticians, to obtain breast tissue samples from a large number of high-risk women and then analyze gene expression in different breast cell types, took five years to complete. A unique study in the field of breast cancer research for its focus on risk prediction and prevention rather than cure of the disease, it was published in the journal Cell Stem Cell in June this year.

……in reality, preventing cancer can have the biggest impact on cancer-associated morbidity and mortality,” Polyak said. “……breast cancer affects so many women, and even though many of them are not dying of breast cancer, there’s a significant personal and societal burden.”

Stem Cells and Cancer Research – The Results

A small proportion of tumour cells have the capacity to initiate and maintain a malignant tumour. These cells have stem cell properties, also called progenitor cells, and can be identified and sorted. While recent investigations had indicated that breast cancer risk factors can alter the number and properties of mammary gland stem cells, the effect of pregnancy on the number and properties of these stem cells had not yet been analyzed in humans.

The researchers with Polyak and Sukumar studied cell types in breast tissue from three groups of women, those who had a full term pregnancy, those who did not, and women with BRCA1/BRCA2 mutations, to identify cells with stem-like characteristics in breast tissue.

The researchers found a significant difference in the number of stem cells in women without BRCA1/BRCA2 mutations, who have had a full term pregnancy. Cancer-free women who had never been pregnant had higher counts of mammary gland stem cells than women who had a full term pregnancy – meaning that pregnancy reduced the number of cancer progenitor cells. BRCA1/BRCA2 mutation carriers had higher number of stem cells than cancer-free women, even when they had carried a child to term, implying that the changes that occur during pregnancy do not occur in women with genetic predisposition to cancer.

Specifically stem cells positive for the p27 biomarker were identified as a potential breast cancer progenitor cells. The researchers hypothesize that a decrease in the population of p27+ cells after carrying a child to term is probably due to decreased activity of stem-cell related signalling pathway after pregnancy.

Identification of Markers & Targets for Chemoprevention

As early pregnancy specifically decreases the risk for estrogen receptor-positive breast tumours, the ultimate goal of the study was to identify targets for chemoprevention that would mimic the cancer-protective effects of pregnancy. The authors believe the signalling pathways they have identified might be exploited for breast cancer prevention because their modulation could deplete p27+ progenitors and decrease breast cancer risk.

…..we can use a progenitor cell census to determine who’s at particularly high risk for breast cancer,” said Polyak, “We could use this strategy to decrease cancer risk because we know what regulates the proliferation of these cells, and we could deplete them from the breast.”

The researchers are now testing p27 as a mammary gland stem marker on thousands of tissue samples collected from women with well recorded medical history to verify if it is an accurate breast cancer predictor in a large population. If the hypothesis is proved correct, Polyak says the commercial development of a clinical test for breast cancer risk would follow.

WHAT’S NEXT?

If you would like to learn more about disease prediction, continue reading this related blog post: “How To Choose a Genetic Testing Provider”.

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