The article entitled MammaryGland Architecture as a Determining Facter in the Susceptability of the HumanBreast to Cancer, by Jose Russo, focuses on a study done with 3 different
classes of patients and the type of breast tissue they exhibit. The first
group, the control, were women undergoing reduction mammoplasty (RM), the
second undergoing a mastectomy due to genetic familial breast cancer (FAM), and
the third group were women who underwent a radical mastectomy due to invasive
carcinoma (MRM). Russo postulates that the development and design of the breast
tissue plays a part in the likelihood of developing cancer. To understand this
we must first look at the types of breast tissue that exist.
There are 4 breast tissue types discussed by Russo, lob 1,
lob 2, lob 3 and lob 4. Lob 1 tissue is the most undifferentiated and comprises the
most distal end of the breast. This is much like normal epithelial tissue and is
developing all throughout a woman’s life until the end of the first complete pregnancy.
Lob 2 is the next stage after lob 1 and has a slightly more complex structure.
Lob 3 and lob 4 have many more ductules per lobule, and lob 4 has lactation
capacity. The lobules progress inward from the nipple, and lobules 2-4 are developed when the hormones of pregnancy are introduced. Russo also explains that there are many hormone receptors on the lob 1 cells, which is why they can proliferate so easily and rapidly. However, the more advanced the lob type, the lower number of hormone receptors found on the cells.
Russo’s hypothesis is that because there are significantly
more estrogen and progesterone receptors on the lob 1 cells and they have the
highest rate of proliferation, they are more easily targeted by carcinogens and
adapted into cancer cells. The lob 2-4 cells have very few hormone receptors and
are not rapidly proliferating, so they are less likely to become cancer cells.
Because lob 2-4 develop in response to pregnancy, Russo also believes that parous
women are less likely to get breast cancer because the more differentiated tissues developed do not
mutate as easily as lob 1. This is shown in table 1. The parous RM women have a mean lob 1 tissue percentage of only 16.9, whereas the FAM and MRM nulliparous woman have a much higher lob 1 percentage of 51.3 and 80. This shows that lob 1 is associated with cancer. The issue I have with this table is that the standard deviations are just as large as the actual percentages in many cases, which makes this data not as reliable as the author portrays it. This could point to many outliers and makes me skeptical, wanting to see each individuals report.
The data shown in the table of Russo’s paper is significant
and shows a strong correlation between parity and decreased risk of breast
cancer (p<0.0005). It also makes sense given the context of what we have discussed in
class thus far. The lob 1 cells have a short turnover time and are easily
impacted by epigenetic factors, which could be methylation of the DNA in lob 1 or bulky adducts added from carcinogens. This correlation has been shown epidemiologically for years, as seen in the cancer statistics on the National Cancer Institute website. However, Russo doesn’t really ever go into
detail about the exact mechanism of how these more differentiated lob types
confer resistance to carcinogenic agents. I would be curious to see if there is
an answer to that or if it is still unknown. Russo also doesn’t go into the
specifics of the hormone receptors mentioned in the lob 1 cells. I would like
to know more about those receptors and the impact that estrogen and progesterone have on the different lob cell types.
He also says that pregnancy “primes” the cells of the breast tissue so they
won’t proliferate out of control. What does this priming entail and is this a
possible solution to lowering the breast cancer rate as a whole, if every woman
could potentially be injected with a hormone cocktail that did the same
preventative task as pregnancy? Ultimately, this article leaves me wanting to know more and with many good research questions about the mechanisms implored by the lob 2,3,and 4 cells of human breast tissue that help defend a person from obtaining breast cancer.
Russo, J., Lynch, H. and Russo, I. H. (2001), Mammary Gland Architecture as a Determining Factor in the Susceptibility of the Human Breast to Cancer. The Breast Journal, 7: 278–291. doi: 10.1046/j.1524-4741.2001.21033.x
"Reproductive History and Breast Cancer Risk - National Cancer Institute." Reproductive History and Breast Cancer Risk - National Cancer Institute. National Cancer Institute, 10 May 2011. Web. 18 Apr. 2014. <http://www.cancer.gov/cancertopics/factsheet/Risk/reproductive-history>.
