Breast tissue...of increasing importance

With increasing cases of breast cancer in today's female population the knowledge of breast tissue is of upmost importance. SEE "OLDER POSTS" TO ACCESS REFERENCES

Tuesday, March 25, 2008

Analysis of Paper

The normal breast and its variations in mammography (2005). J. Stines & H. Tristant. European Journal of Radiology. 54: 26-36.

The Paper’s Findings

Unlike other scientific papers with a study and an objective, this particular paper is not an experimental study. This paper focuses on the breast as a whole including their origin, how they change throughout a woman’s life and how they are analyzed via a mammogram. The paper is a collection of facts and information from various sources that meld together to give a comprehensive view of the study and diagnosis of breasts including factors that make it more difficult to analyze mammograms. So, there are really no ‘results’ to report as no experiment was conducted. However, there were many important facts to take from this paper that could be considered results.
First, how the breasts begin development was described beginning with in the womb and continuing up to puberty. This description was more of background information for the readers. Next, the different components of the breasts were described in terms of how they appear on a mammogram. A mammograph is a technique that uses a tissues absorbance of X-ray waves to gain an inside look at the tissues of the breast. This method is used in diagnosis of problems with the breast including determinations of tumors or cancers. First it was explained that the mammogram is result of summation of all anatomical structures of the breast, which is a three dimensional structure itself. The greater the amount of fatty tissue in the breast, the better the view of the fibrous tissue. The difference between the two tissues is called radiological contrast which is the ability of one type of tissue to absorb more or less radiation waves than the other, thus making it visibly distinguishable. To increase this contrast and gain a better view of the breast molybdenum target is used which affects filtration of waves and the overall output. Also, a grid with low kilovoltage is used which increases the exposure time to the waves.
An important factor with the mammogram is hydratation of the breast. This refers to the fatty content that was mentioned briefly earlier. Again, the more fatty tissue present the better the view of the breast. Denser tissue, like the tissue present in younger females, is harder for the waves to penetrate and thus harder to gain a picture. This makes diagnosis of younger females more difficult as the tissue is denser and gives hard to read pictures. It was also stated in the paper that generally the denser the tissue the higher the associated risk with breast cancer, which is disheartening as dense tissue is harder to diagnose. With this in mind there are also problems associated with mammography. Firstly, when a lower kilovoltage is used to gain a better look it comes with the price of blurring if the patients moves, thus compromising the picture. Secondly, the topography of the breast itself causes problems. Due to the rounded shape and the curvature of the chest wall one mammogram will never give a complete view of the entire gland or all the tissues. Two methods are therefore used to view the breast – the oblique view and the lateral view. The oblique view is not really used anymore and the lateral view is more widely adopted. This view unfortunately does not detect cancer, but does help give the precise location of lesions. Another well known problem with the mammogram is its difficulties in distinguishing between normal fibrous structural components and tumor growth.
Next the paper went into different abnormalities in breasts which ranged from size abnormalities to nipple abnormalities. The paper went a step further by describing the mammographic difficulties and how to evaluate these conditions. For example, hypertrophy is a condition described by rapid growth within months and is linked to increased sensitivity to estrogen receptors responsible for growth. This can be analyzed by a craniocaudal view.
The next section of this paper covers variations in the breast density due to age, menstrual cycle, pregnancy and hormonal treatment. In terms of age, it is found that as woman age their breast density decreases, making it easier to pick up on cancer abnormalities as there is less dense tissue to block the view. In the second part of the menstrual cycle the density is increased, which decreases accuracy of the mammogram. As the breasts grow very quickly with pregnancy the glandular tissue expands. However, the density does not always increase, therefore mammograms can still be useful in diagnosis. Hormonal treatments can also change the density of breasts. These treatments usually reduce breast density, however if these treatments are implemented after a long period without hormonal prescription the density can increase.
The very last section of the paper briefly discusses the false positives associated with mammograms. The risk of false positives increases with the density of the breast from 1.7 when the breast is covered in 5-24% of dense tissue to 4.3 if the breast is covered in 65% or more dense tissue.

Analysis of the paper

From a reader’s perspective the paper was easy to read and understand. It also contained a lot of valuable information that every woman needs to know, including the general gist of the mammogram itself and how important it is in diagnoses. This paper also approached different developmental stages of a woman’s life and explained how each one changes in terms of breast density and how this affects mammograms. The abnormality section was interesting and additional information that rounded off the paper.
I found the tables useful, especially Table 4 which described the different photographic aspects of the mammogram. Another interesting table was Table 3 which gave densities of everyday entities such as water and vegetal oil as a means of comparison to understand the densities of different mammary structures. The pictures were great in the fact that they compared different types of tissues and depicted what the differences are.
So, in terms of the results I think that the facts are all nicely summarized in the tables and the pictures certainly help clarify some of the conditions described throughout the paper.

Saturday, January 26, 2008

Breasts and their function

A sign of fertility, the mark of life-giving milk. These are quotes used in earlier times to describe a woman's breasts. Ancient paintings and representations of woman goddesses often emphasized the breasts as the sign of motherhood and child-bearing. Today, the way one views a woman certainly has changed to a more independent and liberal outlook but the function of the breasts in procreation still remains the same - they are vital to the nourishment and immunity of a newborn child. Through the lactation of breast milk infants are provided with a mixture of lactose, fats, ions, vitamins, immunoglobulin A and casein which binds calcium. [1]

Basic Anatomy of the Breast

The basic layout of the breast is shown in this simplified diagram depicting the nipple, which is raised, and the areola which is the darker circle. The nipple usually extends a few millimeters from the breast and is surrounded by the areola. Areola, like the nipple, varies in diameter but is usually between 1.5-2.5mm. The dotted like structures on the areola are modified apocrine glands, sweat glands and sebaceous glands [2]. The dark pigmentation seen in the areola is due to the network of capillaries that carry blood very close to the surface. This dark colour first appears more apparent at puberty and also darkens again during pregnancy[2].

Stages of Breast Development

How it all begins

Believe it or not, breast development begins within the wound as early as the 4th week of life as a fetus. Breasts are ectodermally derived and first begin as
thickenings of the epidermis that extend from the armpit to the groin forming the 'mammary lines' or 'milk lines' [2]. By the 9th week, the milk lines are reduced to the chest area leaving only 2 bud like structures. Primitive vessels develop and near the 13th week the nipple as well as areola appear[3].


The mammary gland is present as a disk of about 1 cm in thickness. From here on in the breasts remain dormant while the mammary glands change with lobes and galactophores (ducts in the breast) beginning to form [3].


The stages just before development and during are summed up into 5 stages as originally proposed by Tanner [4]:
Stage 1: Preadolescent: Tip of the nipple is raised
Stage 2: Buds appear, now the breast is raised as well. The areola enlarges
Stage 3: Breasts are a little larger and some glandular tissue is present
Stage 4: Areola and nipple are now raised which form a mound
Stage 5: Mature Adult: Breast round and only the nipple is raised

A more indepth view of the breast

Breasts are composed of two major tissue types:
1) glandular tissue - responsible for the mammary glands which produces milk
2) adipose tissue - fatty tissue

The adipose tissue is considered subcutaneous and lie under the skin of the breast. Glandular tissue is located in front of the pectoral muscle[5].The mammary glands are from cutaneous origin. They consist of a network of tubules called lactiferous ducts which are supported by loose connective tissue followed by dense connective tissue and adipose tissue. The dense tissue divides into septa between the ducts divide the mammary gland into lobes [2]. These lobes are made up of lobules which contain alveoli. These alveoli also are composed of lactocytes which are secretory epithelial cells responsible for the secretion of breast milk [5]. Structurally the alveoli are connected to the smaller ducts which join together to form larger ducts draining the lobules. The larger ducts also join into one milk duct for each lobe that eventually ends in the lactiferous sinus which is the opening of the nipple [5]. The ducts themselves consist of stratified cuboidal epithelium which is made up of inner secretory cells and outer myoepithelial cells [1] while the inner sinus in the nipple is lined with a double layer of stratified cuboidal epithelium. As the outside of the nipple is reached the tissue gradually gives rise to keratinized stratified squamous epithelium [2].

Figure 2: Nonlactating breast showing lactiferous ducts, loose connective tissue, dense connective tissue and adipose tissue [1]
Figure 3: A closer look at a lactiferous duct [2]

The areola is covered with a thin layer of stratified squamous epithelium. This layer contains keratin and is continous over the entire breast, including the exterior of the nipple. The dermis, comprised of elastic connective tissue, extends deep into the skin and forms irregular dermal papillae [2].

Figure 4: A closer look at the nipple [2]


Mammary glands resemble sweat glands and are actually derivatives of eccrine sweat glands[1]

The transformation of breasts during pregnancy

During pregnancy

If you have ever been pregnant or know someone who has been, one of the obvious transformations during pregnancy (besides the belly of course!) is the breasts.
During pregnancy the body produces hormones such as estrogen, progesterone, prolactin, human chorionic somatomammotrophin, thyroid hormone and corticosteroids. The secretion of these hormones by the placental and corpus luteum causes the terminal duct epithelium in the breasts to grow and more secretory acini to be developed [6]. Inner secretory cells in the breast tissue also become bigger and the alveoli eventually contain breast milk [1].

Figure 5: a) The lobules (Lo) have enlarged while the septa (S) remain the same size while dividing the breast into lobes. b) acini (A) are dilated and the epithelial cells (E) show cuboidal structure as well as low columnar. The dilation of the acini and the ducts is due to the accumulation of colostrum [6].Colostrum is the first secretion of the breasts after pregnancy. It consists of a laxative and maternal antibodies.

When a women begins lactating the breast again changes.
Figure 6: The lactating breast. The important feature to take from this is the myoepithelial cells (M) which are the secretory cells that contract to actually expel the milk. The lipid droplets (L) also seem to take up a large amount of space and are discharged in apocrine secretion [6], which could account for why breast milk is so high in fatty content. IgA, produced by plasma cells in the connective tissue surrounding alveoli [1], is also released into the milk via transcytosis by the small vesicles (V). Protein is developed by the rough endoplasmic recticulum (rER) and small protein granules can be seen by the black dots in the micrograph [6].


Once the baby is born and begins suckling the breast, two neurohormonal reflexes occur:
1) prolactin is released by the anterior pituitary which stimulates milk production [6]
2) oxytocin is released by the posterior pituitary which causes myoepithelial cells to contract. These cells are located around the secretory acini and ducts, so it causes milk to be pushed down the ducts and eventually out the nipple [6]

If suckling stops then these hormones are not released and the lactating breast regresses [6].


For effective output of the milk, it is suggested that the baby should have a large portion of the areola in the mouth [5].

A Breast's Worst Enemy

Cancer is when our cells proliferate out of control forming large masses or lumps called tumors. If cancerous cells reach the blood stream or lymphatic tissue they can migrate to other parts of the body [7]. Tumors can be either benign, where they remain in one place and do not threaten the person's health, or malignant where they move to other places in the body and invade surrounding cells [7].
In women, cancer of the breast is the most common malignancy [8]. Statistically approximately 1 in 10 women will develop a form of breast cancer [1], which can be a scary thought when sitting in a class surrounded by 20 or more women. Alot of breast tumors arise from the epithelium of lactiferous ducts ( Ductal Carcinoma) and are treated by surgical procedures that cut out that portion of the breast to stop the cancerous cells from spreading into circulation [1]. Other types of cancer are caused by mutations in various proteins. One particular protein that suppresses the formation of tumors is BRCA1/BRCA2. When mutations occur in these proteins the chance of developing cancer is heightened. About 5-10% of all types of breast cancer originate from mutations in these important proteins [1].
HER2 is another important protein that regulations cell proliferation. Mutation in this protein also increases the risk of cells dividing out of control. 30% of cancers are associated with mutation in this protein [1].

Factors increasing likelihood of breast cancer [7]

  • If you have a family history of breast or ovarian cancer or if you have had cancer before.
  • If you have never had children or gave birth for the first time after 30
  • Began menstruation early or reached menopause late
  • If you had hormone replacement therapy (exposure to increased amounts of estrogen)
  • If you have denser breast tissue
  • If you are obese, drink alcohol, or are on the 'pill'
What are the signs of breast cancer? [7]
  • lump in the armpit
  • changes in your breasts including shape and size
  • swelling, redness and a warm feeling in your breast(s)
  • puckering of the skin, inverted nipple (This is only dangerous if it is a new condition [3])
  • scaling on the nipple
Diagnosis of breast cancer [8]
Keep in mind that if you have symptoms you may not have breast cancer, these symptoms are not uncommon in a normal woman. Usually further analysis is needed for a certain diagnosis. One method used is a 'triple assessment'. This includes three main assessments before reaching a decision: a clinical assessment, imaging (ie. a mammogram, ultrasound) and closer look at the cytology of the cells through a fine needle aspiration, a needle core biopsy or a breast core biopsy. However, methods are not always 100% certain. Tests may need to be completed more than once so your doctor can be sure of the condition of your breasts.
Treatment of breast cancer

Once diagnosed treatment generally follows similar trend to treatment of other cancers and can include [7]:
  • surgery
  • chemotherapy
  • hormone therapy
  • biological therapy
  • radiation therapy
Some other notable treatments have been developed. One is the use of an antiestrogen compound called "tamoxifen". This acts by binding to estrogen receptors and changing its shape so certain steroid co-activator proteins cannot bind, and DNA transcription cannot occur. Hence cells cannot proliferate [1]. Antibodies to the HER2 protein mentioned above have been developed and found successful in preventing mutations in this protein.

So how can you protect yourself?
Follow the seven steps to Health, outlined by the Cancer Society [7]:

1) Don't smoke and avoid second hand smoke

2) Eat right

3) Get active!

4) Protect yourself from the sun

5) Follow cancer screening guidelines

6) Visit your doctor regularly

7) Follow hazardous and safety instructions

Breast Self-Examination

Following these simple steps can keep you up to date on your health. If done on a regular basis you can easily recognize any changes in the shape or size of your breast. More information can be found at the Forrest General Hospital Cancer Services

7 P's of a Good BSE
1. Positions

* First, stand in front of a mirror with your arms relaxed at your side.
* Then place your hands on your hips.
* Raise arms above your head.
* Bend slightly forward, allowing your arms to hang freely toward the floor.

In each position, look for changes in contour and shape of the breast, color and texture of the skin and nipple, and evidence of discharge from the nipples.
Palpation: Side-lying and flat:

* Use your left hand to palpate the right breast, while holding your right arm at a right angle to the rib cage, with the elbow bent.
* Repeat the procedure on the other side.
* The side-lying position allows a woman, especially one with large breasts, to most effectively examine the outer half of the breast. Do this by lying on the opposite side of the breast to be examined. Rotate the shoulder (on the same side as the breast to be examined) back to the flat surface.
* A woman with small breasts may only need the flat position. Lie flat on your back with a pillow or folded towel under the shoulder of the breast to be examined.

2. Perimeter

Visualize the perimeter of the breast as an imaginary line which extends down from the middle of the armpit to just beneath the breast. The imaginary line continues across along the underside of the breast to the middle of the breast bone, then moves up to and along the collar bone and back to the middle of the armpit. Most breast cancers occur in the upper outer section of this area (towards the shoulder and armpit).
3. Palpation

With Pads of the Fingers: Use the pads of three or four fingers to examine every inch of your breast tissue. Move your fingers in circles about the size of a dime. Do not lift your fingers from your breast between palpations. You can use powder or lotion to help your fingers glide from one spot to the next.
4. Pressure

Use varying levels of pressure for each palpation, from light to deep, to examine the full thickness of your breast tissue. Using pressure will not injure the breast.
5. Pattern of Search

Use one of the following search patterns to examine all of your breast tissue. Palpate carefully beneath the nipple. Any incision should also be carefully examined from end to end. Women who have had any breast surgery should still examine the entire area of the incision:

* Vertical Strip: Start in the armpit, proceed downward to the lower boundary. Move a finger's width toward the middle and continue palpating upward until you reach the collarbone. Repeat this until you have covered all breast tissue. Make at least six strips (passes with your fingers) before the nipple and four strips after the nipple. You may need between 10 and 16 strips.
* Wedge: Imagine your breast divided like the spokes of a wheel. Examine each separate segment, moving from the outside boundary toward the nipple. Slide fingers back to the boundary, move over a finger's width and repeat this procedure until you have covered all breast tissue. You may need between 10 and 16 segments.
* Circle: Imagine your breast as the face of a clock. Start at 12 o'clock and palpate along the boundary of each circle until you return to your starting point. Then move down a finger's width and continue palpating in ever smaller circles until you reach the nipple. Depending on the size of your breast, you may need eight to 10 circles.

6. Practice With Feedback

It is important that you perform a BSE while your instructor watches to be sure you are doing it correctly. Practice your skills under supervision until you feel comfortable and confident.
7. Plan of Action

Every woman should have a personal breast health plan of action:

* Discuss the American Cancer Society breast cancer detection guidelines with your health care professional.
* Schedule your clinical breast examination and mammogram as appropriate.
* Perform a BSE monthly. Ask your health professional for feedback on your BSE skills.
* Report any changes in your breast to your health care professional.

Myths of Breast Cancer

It seems like every year we find more and more factors contributing to cancer. However, among all this information are some beliefs concerning breast cancer that are actually MYTHS [10]

1) Men can't get breast cancer
2) Underwire bras cause breast cancer
3) Women under 40 don't get breast cancer
4) Deoderants cause breast cancer
5) Birth Control Pills cause cancer (although there has been studies showing slight association [7] there is no direct link)
6) Mammograms spread breast cancer
7) A lump in the breast is always breast cancer
8) Breast cancer can only develop in one breast, not both
9) A mastetomy is the only treatment
10) The smaller the your breasts the smaller the chance of developing breast cancer

Associated links to breast cancer, definitely worth a look:

Canadian Cancer Society
All About Breast Cancer
Health Canada
Breast Cancer Society of Cancer
The Weekend to End Breast Cancer

At our own university there is a comprehensive Masters in Science program in Medicine that specializes in cancer research. Some of the supervisors specialize in breast cancer research and are strong supporters of breast cancer research. Dr. Jon Church in particular has made tremendous efforts to help those with breast cancer. He owns and administrates an internet discussion listserv called "BREAST-CANCER" where over 600 people from 30 countries can discuss topics on breast cancer. He also uses an audio teleconference twice a month as a means of support for woman suffering from breast cancer and coordinates a world wide web page that was recognized in 1997 by Snap! Online and HealthyWay as " Best of the Web".
Dr. Gary Paterno is another researcher at Memorial that completes work directed towards breast cancer. He currently is studying the regulation of estrogen receptor activity and it's role in breast cancer.