Tuesday, November 25, 2008

Breast Maturity & Breast Cancer Risk

A breast development that affects breast cancer risk is the maturation of breast lobules from Type 1 lobules to Type 4 lobules. Breasts are composed of units of breast tissue called lobules and are surrounded by supportive tissue made of fat and stromal (connective) tissue. A lobule is composed of a milk duct with surrounding ductules which are the glands that make the milk. Lobules are in turn composed of individual breast cells.

At birth, you have a small amount of breast tissue, Type 1 lobules, which are very immature and are known as TDLUs (terminal ductal lobular units). Ductal cancers which account for 85% of all breast cancers are known to arise in Type 1 lobules. An infant’s breast tissue may be stimulated by the mother’s hormones present in the infant at birth. This can cause a milky secretion called “witch’s milk” for a short time after birth. At puberty, in response to the cyclic elevations of estrogen and progesterone, the breasts start to develop further, and some Type 1 lobules are matured into Type 2 lobules, which have more ductules per lobular unit.2 lobules are where up to 15% of all breast cancers start. By the end of puberty, about 75% of breast tissue is Type 1 lobules and 25% are Type 2.

Full maturation and cancer resistant Type 4 lobules are not formed until late in pregnancy when the breast is under the influence of the pheromones hCG and hPL which are made by the fetus and placenta in the womb. Type 4 lobules contain colostrum, the first milk. By mid 2nd trimester 70% of the breast tissue is Type 4 lobules, and at 40 weeks (full-term), 85% is Type 4 and cancer resistant. After weaning, the Type 4 lobules regress to Type 3, but remain cancer resistant due to permanent genetic changes which have made them cancer resistant. Each subsequent pregnancy after the first matures more of the breast tissue resulting in a further decrease in breast cancer risk of 10%.

Not only do these lobules look different anatomically, but they grow differently. For example, Type 1 and 2 lobules copy their DNA faster than Type 3 lobules. The faster DNA is copied, the higher the risk of mutations or cancer cells forming.

Actual photomicrographs of human breast lobules:

Type 1 Lobule
Type 3 Lobule

The principle of breast cancer risk relating to lobule maturity can explain other well-documented breast cancer risks as well.

If a woman does not have a full-term pregnancy (meaning she is childless or ), she has increased risk for breast cancer, since she never develops Type 4 lobules. If she has children later in life (after age 30), she has increased risk, because, for most of her menstrual life, her estrogen has been stimulating immature Type 1 and 2 breast lobules. If she has children as a teenager, she has decreased risk of breast cancer, since her breast tissue matures very early in her reproductive life to Type 4 lobules.

If a woman breast-feeds, she often has (in which estrogen is low) or misses menstrual altogether. She has decreased risk due to two factors: less exposure to estrogen and breast tissue maturity to Type 4 lobules. Risk decreases in proportion to duration of breastfeeding.

The risk factors of estrogen exposure and breast immaturity can also act in concert with one another, causing greater risk. For example, if a teenager, who has not had a full-term pregnancy (she is nulliparous), takes birth control pills, her risk of breast cancer is much higher than it is for a woman who has had several children and then takes birth control pills. A woman who gets pregnant increases her estrogen level 2,000 percent by the end of the first trimester. If her pregnancy goes to full term, she will have lower breast cancer risk by developing full breast maturity. If it ends before 32 weeks, by very premature birth or , she will have increased risk as she will not get the benefit of full breast maturation, but instead be left with more places for breast cancer to start. in the first trimester do not increase breast cancer risk because they are associated with low estrogen levels.

Cigarette smoking before a full-term pregnancy can increase a teenager’s breast cancer risk substantially, because her breast lobules are immature and rapidly growing.