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Thursday, January 19, 2012

Breast pain / lumps in women


Mammography. Radiopaedia
Author : Richard J. Santen Endocrinologist University of Virginia, Charlottesville, VA 2008-06-10(Underlined words are defined in the Glossary at the end of this article).

When considering problems of breast pain or lumps, one must first understand how the breast is influenced by hormones during the pre-and post-menopausal years. The important hormones with respect to the breast are the estrogens and progesterone.  There are three estrogens, estrone, estradiol and estriol, but estradiol is the major one that is active on breast tissue. Progesterone is made and released mainly during the second half of the menstrual (monthly) cycle. Estradiol and progesterone work together to stimulate the growth of tissue in the breast.







At the time of puberty, the master gland in the body, called the pituitary, causes the ovary to begin making female hormones. This begins at about age 11-13 and results in an increase in levels of estradiol in the blood.  As the breast develops, two types of structures are formed, ducts and lobes (see Figure 1).  Ducts are small tube like structures in the breast that carry milk to the nipple in women who are nursing. The lobes consist of glandular tissue which represents the cells of the breast that produce milk at the time of breastfeeding. Broadly summarized, estrogen mediates the development and elongation of ductal tissue and progesterone facilitates ductal branching and lobular development. At the time of late pregnancy, another hormone, prolactin, the milk producing hormone, is also made by the pituitary to stimulate milk production.

The appearance of breast tissue under the microscope (histologic appearance) changes as a woman progresses from puberty until the menopause. As a woman gets older, the supporting tissue (stromal and fat cells) increases and there may be an enlargement in the size of the lobules and fluid filled sacs; other fluid filled structures called cysts, become more frequent.  For many years this normal process which progressed with age was not recognized and physicians called the changes in the breast  “fibrocystic disease.” They made this diagnosis when the breast was lumpy due to the cysts and contained  enlarged lobules and  increased amounts of stroma. However, since up to 60 % of women have these changes, it was later recognized that this is a normal process which is now called by the modern term “fibrocystic changes”(1). The term “fibrocystic disease” is still used, but now it refers arbitrarily  to women with a substantial amount of breast pain and more than a usual degree of lumps, which may require biopsy (2). It is important to know that women with  fibrocystic changes have no increased risk of breast cancer later in life as a result of these changes (3).   
 

Lumps in the breast




In women between the age of puberty and the mid-twenties, the lobules and stroma in the breast may respond to hormonal stimuli in an exaggerated fashion with the development of single and multiple benign lumps called fibroadenomas (Table I).  These are very common. When the breast tissues from women dying a traumatic death are examined at autopsy, 15 to 23% of women in this age group are found to have fibroadenomas. In specialized clinics set up to see women with breast lumps, 7 to 13% of women are found to have fibroadenomas.  When seen by primary care physicians for reasons other than breast lumps, 2.2 % of women have fibroadenomas detected on examination (4).  These lumps are very worrisome to women because they are concerned about breast cancer, but women should be reassured because fibroadenomas are quite benign and easily diagnosed by biopsy or even just ultrasound.

Between the ages of 30 and 40, the degree of diffuse palpable nodularity (lumps which can be felt on examination) may increase.  This increase is called  adenosis, which is an increase in the amount of normal  tissue found in the breast lobes  (see Figure 1).   The stroma (supporting tissue in the breast) may also undergo more rapid growth, resulting in  areas of ill-defined fullness, frequently in the part of the breast near the armpit (axillary tail).  In women between the middle of the fourth decade of life and menopause in the early fifties, lobe tissue may undergo further increases in size in association with the presence of more  stromal tissue.  The fluid filled sacs called cysts also increase in prevalence with age. More cysts are found as women approach the menopause, when they use menopausal hormone therapy, and when they have a thin body composition (2).



How are benign breast lumps put into categories?




As a  practical way to classify lumps, experts consider breast lumps that do not increase the risk of breast cancer in one category.  Those  that are associated with a small increase in risk (one and one half to two times greater than normal) and moderate risk (more than two times normal)  are put into another category. The various types of lumps and their risk for breast cancer are listed in Table I. In general, the risk of breast cancer increases as the rate of cell growth in the lumps increases (Table II). The risk of breast cancer is also greater if there is more than one lesion or lump present
 

Table I.  Classification of Benign Breast Lesion Histology



Breast Cancer Risk

No Increase
Small Increase (RR 1.5 – 2.0)
Moderate Increase (RR>2.0)
Fibrocystic changes - aberrations within
range of normal
Pathologic lesions
·         Usual ductal hyperplasia
·         Complex fibroadenoma (containing >3mm cysts, sclerosing adenosis, epithelial calcifications or papillary apocrine changes)
·         Papilloma or papillomatosis
·         Radial scar
·         Blunt duct adenosis
·         Atypical ductal hyperplasia
·         Atypical lobular hyperplasia
·         Cysts and duct ectasia (72%)a
·         Mild hyperplasia (40%)a
·         Non-sclerosing adenosis (22%)a
·         Periductal fibrosis (16%)a
·         Simple fibroadenoma (15-23%)b
·         Sclerosing adenosis (3.1%)a
·         Miscellaneous (NA)
-         Lobular hyperplasia
-         Juvenile hypertrophy
-         Stromal hyperplasia
·         Benign tumors
-         Hamartoma
-         Lipoma
-         Phyllodes tumor (benign) c
-         Solitary papilloma
-         Neurofibroma
-         Giant fibroadenoma
-         Adenomyoepithelioma
·         Traumatic
-         Hematoma
-         Fat necrosis
-         Foreign body
·         Infection
-         Granuloma
-         Mastitis
·         Sarcoidosis
·         Metaplasia
-         Squamous
-         Apocrine
·         Diabetic mastopathy



a.        Sandison AT. An autopsy study of the adult human breast; with special  reference to proliferative epithelial changes of importance in the pathology of the breast 

National Cancer institute Monograph No. 8 1962: 1-90; percent (% ) refers to the percentage of autopsied breasts in whom the lesion was found

b.        Goehring C, Morabia A. Epidemiology of benign breast disease, with special attention to histologic types. Epidemiologic Rev. 1997; 19: 310-327.

c.        Most phyllodes tumors are considered to be benign ibroepithelial  tumors but some have malignant clinical and histological features
     

Table II.  Classification Of Common Benign Breast Disorders In Women


Pain
Breast pain
Cyclic
·         Hormonal stimulation of normal breast lobules prior to menses
Non-cyclic
·         Stretching of Cooper’s ligaments
·         Pressure from a brassiere
·         Fat necrosis from trauma
·         Hydradenitis suppurativa
·         Focal mastitis
·         Periductal mastitis
·         Cyst
·         Mondor’s disease (thrombophlebitis of breast veins)
Non-breast pain
Chest wall pain
·         Tietze’s syndrome (costochondritis)
·         Localized lateral chest wall pain
·         Diffuse lateral chest wall pain
·         Radicular pain from cervical arthritis
Non-chest wall pain
·         Gall bladder disease
·         Ischemic heart disease
Nipple Dis-charge*
Galac-torrhea
·         Arising from multiple ducts bilaterally
·         Hyperprolactinemia from pituitary tumor, hypothyroidism, drugs (see list in standard textbooks)
Non-galac-torrhea
·         One duct
·         Elicited or spontaneous and  bloody, occult blood,  or serosanginous
·         Intraductal papilloma
·         Ductal carcinoma in situ
·         Paget’s disease of breast
·         Multiple ducts
·         Elicited and  non-bloody, bilateral, black or clear discharge
·         Fibrocystic changes
·         Duct ectasia
Discrete solitary lump
< age 30
·         Firm, rubbery
·         Most common lesion: fibroadenoma
Age 30-50
·         Firm, discrete
·         Most common lesions:fibroadenomas, cysts, fibrocystic changes, UDH, ADH, ALH (UDH, ADH, ALH  are also  found incidentally in women undergoing biopsy for masses representing other etiologies such as fibroadenomas and fibrocystic changes)
> age 50
·         Firm, discrete
Most common lesions: cyst, DCIS, invasive cancer
Diffuse lump-iness
“lumpy-bumpy”
·         Absence of discrete lump
·         Fibrocystic changes

* considered pathologic if spontaneous
 

How do doctors know what the risk is from breast lumps?




The levels of risk in women with various types of lumps have been established by means of long-term follow-up.  All lumps are taken out and looked at under the microscope and then the women are observed over several years to see if cancer develops some years later.  The names and specific types of  lumps were defined by  a scientific conference (consensus conference) organized to come to agreement about the names of these lumps and how to identify them (5).  



What causes benign breast lumps?




Observations in women receiving estrogens and anti-estrogen drugs suggest that hormonal events play a positive role in the development of benign lesions.  Among post-menopausal women receiving estrogens with or without progestins as menopausal hormone therapy for more than eight years,  benign breast lesions increase by a factor of 1.7 (6).  The anti-estrogen drug tamoxifen, when used in the prevention of breast cancer (see section on “breast cancer prevention” later in this Knol) is associated with a reduction of 28% in the prevalence of benign breast lesions. This was found when the women who developed breast cancer while on tamoxifen had their cancers removed surgically and it was possible then to look at breast tissue under the microscope. In the areas of the breast that were far away from the cancer, there was a reduction in the number of benign breast lesions (7). Mutations in genes that occur after birth (called acquired mutations) are also associated with benign breast lesions. In patients with such mutations, these lumps are frequently multifocal, which means that several lumps may be present in the same patient (8).  Women with a family history of breast cancer have a high frequency of multiple benign breast lesions. While familial and hormonal factors can play a role, the cause of the breast lumps is just not known in some women.  



Do benign lumps ever progress to cancer?




Breast lesions are believed by many experts to gradually progress through several stages, but not all lesions progress through all stages. In fact, the number of early stage lesions that go on to become cancer is very small.

At the earliest stages, breast lesions cannot be felt, but are found under the microscope when a biopsy is performed either because of an abnormality on mammogram or another reason. The first stage is called unfolded lobules, which can go on to atypical ductal hyperplasia and then to ductal carcinoma in situ (DCIS) and invasive cancer.

When atypical ductal hyperplasia is present, progression to breast cancer is more common. The lobules in the breast can also progressively change over time from typical lobular hyperplasia to atypical lobular hyperplasia to lobular carcinoma in situ to frank invasive lobular cancer. Having these high risk benign lesions, such as atypical ductal hyperplasia, predisposes one to having a cancer develop somewhere else in the same breast and not necessarily in the same place as the original lesion.  Atypical lobular hyperplasia is associated with an increased risk of breast cancer in the opposite breast as well (3). The fact that the presence of these lesions is associated with changes elsewhere in the breast has led to the concept of a “field defect or mutator phenotype”(2). This is a scientific way of saying that there is something abnormal about the breast tissue, which causes lesions to form in many different places. 
 

What  symptoms can be present when breast lumps are present   and what causes these symptoms?




Breast pain




Breast pain usually occurs in association with the time of the menstrual cycle (9). This pain usually has its onset during the last half of the menstrual cycle. It may or may not occur in association with PMS (premenstrual syndrome) and usually goes away one to three days after the beginning of  monthly bleeding (10).  In a study of 1171 healthy, pre-menopausal, American women, 11% had moderate to severe cyclic breast pain and 58% had mild discomfort.  Breast pain interfered with usual sexual activity among 48% of the patients, and interfered with physical activities in 37%, social activities in 12%, and in school activities in 8% (9;11).  Caffeine or a fatty diet are both considered by some to increase breast pain but there is really no good proof of this. Psychological factors could increase the sensation or discomfort from pain, but it has not be proven that these factors cause breast pain.

Pain may not always be related to the time of the menstrual cycle. If relatively constant, the causes are usually due to rib pain or pain over the junction between the breast bone and the ribs. You or your health care provider can find very small areas of tenderness over the ribs or near the breast bone if this type of pain is present.  Sometimes this small area of pain is due to the rupture of a cyst. Acute enlargement of cysts and infection around ducts, a form of mastitis, may cause severe, localized pain with a sudden onset.
 

Non-breast pain




Pain arising from the chest wall may be mistakenly attributed to the breast.  Pain that is limited to a particular area and characterized as burning or knifelike in nature may arise from the chest wall (12).  Several distinct types of pain can be distinguished, including localized or diffuse lateral chest wall pain, pain  arising from arthritis in the vertebra of the neck, and pain from something called Tsetse’s syndrome, which is also called costochondritis(2). This is a form of arthritis affecting the joint between the breast bone and ribs. Your health care provider can examine you carefully to see if these conditions are present.



Nipple discharge




Nipple discharge can be bloody, yellow, blue, green, black, milky, or clear like water and can be thick or thin in consistency (13;14). Among women referred to physicians because of symptoms of a breast disorder, 6.8% have nipple discharge.  Although this symptom is particularly distressing, only 5% of women with discharge   are found to have serious underlying disease. Nipple discharge is considered to be worrisome if it is spontaneous, arises from a single duct, is persistent, and contains blood.  Age is an important factor with respect to the possibility of cancer. Among women with nipple discharge as their only symptoms who were found to have cancer as a cause, 3% were younger than 40 years of age, 10% were between 40 and 60 years, and 32% were older than 60 years(15). Several other causes of breast discharge can be present: milk that continues to leak from the nipple for a long period of time after a woman stops breast feeding; fluid from cysts in the breast that can leak from the nipples and appear black, blue, yellow or clear, and; blood leaking from the nipple, which is usually due to a small benign lesion called a papilloma.



Single and multiple breast lumps:




The causes of breast lumps are different depending on a woman’s age. Women are grouped by less than 30 years of age, 31 to 50 years, or older than 50 years.  On a statistical basis, nine of 10 new nodules in pre-menopausal women are benign.  Pre-menopausal women are those who are still having monthly menstrual periods and usually are under 50 years of age. In the younger group, fibroadenomas are the most common and for the 31-50 year olds, fibrocystic changes are likely.  In the older group, cancer is usually suspected.

 

What abnormalities are associated with an increased risk of breast cancer?


           

When a lump is biopsied, your health care provider can tell you which are the types of conditions that can increase your risk of breast cancer. Any lump that has an increase in the growth rate of cells within it can put you at a higher risk of breast cancer (Table II).  The most worrisome lesions are those called atypical ductal or lobular hyperplasia, particularly if you have a family history of breast cancer as well. Other conditions (such as those listed in the Table II: usual ductal hyperplasia, complex fibroadenoma, papilloma or papillomatosis, radial scar, blunt duct adenosis) can increase the risk as well, but these are much less common (2). There has been some confusion recently about breast cancer risk associated with the most common lumps due to fibrocystic changes. However, a very large study from the Mayo clinic showed that these lesions do not  predispose to breast cancer provided that  the patient does not have  a family history of breast cancer (3).

Breast density on mammographic screening is also a risk factor for breast cancer (16) (Figure 2). Dense breasts contain a higher proportion of stromal and glandular tissue as well as an increased number of lesions classified as usual ductal hyperplasia and atypical ductal hyperplasia. According to classic studies in twins, inherited factors  account for approximately 60% of the variation in breast density among women. Breast density is usually estimated by the radiologist who is reading the mammogram.


Relative  Risk
 
 

How can my individual risk of breast cancer be estimated?




Your health care provider can ask about your family history, whether or not you have had a breast biopsy,  the age that you  went through puberty, and the age that  you had your first baby. With this information, the health care provider can tell you if you are at high or low risk for breast cancer. A method called the Gail Risk Disk can also be used to give you a more precise idea (17). This takes into account your current age, race, family history of breast cancer, age of first menstrual period, age at your first live birth, number of prior breast biopsies, and the type of lesion found on biopsy. The factors are then put into a computer and you are told what percent chance you have to get breast cancer in five years or over your lifetime. Low risk is said to be less than a 1.7% chance of getting breast cancer over five years or 12% over your lifetime. The Breast Cancer Risk Assessment Package CD Version, which contains both English and Spanish language versions of the tool, can be ordered or accessed online at http://www.cancer.gov/publications, or it can be ordered by telephone at 1-800-4CANCER (1-800-422-6237).



How are breast lumps and/or breast pain evaluated?




Your health care provider will ask you a number of questions and do a detailed physical examination, concentrating on the entire breast and chest wall.  Diagnostic studies may then be ordered.  The triple test to evaluate lumps includes palpation (feeling the breast for lumps), mammography (or ultrasound imaging), and biopsy of the lump.  Mammography, often in conjunction with ultrasound examination, is required for evaluation of lesions that can be felt by the fingers and are discrete.  In special cases, magnetic resonance imaging (MRI) – or a new technique called digital mammography – can be used.

                                                                                                            



Treatment


 

Cyclic breast pain




The most important issue in the management of breast pain is to decide whether to treat. In the absence of a large lump or discharge – and when only mild symptoms are present – your health care provider will usually reassure you that nothing is seriously wrong and that no treatment is needed. Up to 60 % of normal women can have some breast pain at the end of the menstrual cycle. Among 85% of women evaluated in large referral clinics specializing in breast pain, watchful waiting without treatment was usually recommended. The remaining 15% of women  requested treatment (2). 

Several clinics specializing in breast disorders administer tamoxifen (an anti-estrogen) and danazol (a weak male hormone) for breast pain and have conducted randomized placebo-controlled clinical trials and  demonstrated  that these types of therapy work (18). Information has also  been obtained  from an international study   involving 7152 women who received tamoxifen (19).  This study provided additional evidence that this drug relieves breast pain. Several other therapies are probably beneficial on the basis of physiologic principles.  Precise fitting of a brassiere  which provides support for pendulous (droopy)  breasts may provide pain relief (20). In women already receiving menopausal hormonal therapy, lowering the dose of estrogen appears to be beneficial in reducing breast pain.  The use of oral contraceptives that contain low-doses of  estrogen  and a progestin  may result in a reduction of pain (21).  Addition of an androgen to estrogen replacement therapy with a preparation such as Estrotest may also be helpful (2).

No standard regimen for moderate to severe  breast pain has been widely accepted.  Initial recommendations may include use of mild pain reducers such as acetaminophen (Tylenol), or nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Motrin) or naproxen (Aleve), or aspirin.  Other approaches include the anti-estrogen tamoxifen for three to six months. In patients in whom there is no response to anti-estrogen  treatment, a change to a drug called  danazol may be helpful and often relieves pain. This is given in either of two ways:  either daily or  just  during the luteal phase of the menstrual cycle. often relieves pain.  Evening Primrose oil has been used, but a recent study questioned whether it worked (22).



Non-cyclic breast pain




When pain is truly arising from the breast, the approach outlined for cyclic pain is used.  However, if the pain is from the ribs or muscles under the breast, drugs such as aspirin, or NSAIDs such as ibuprofen or naproxen can help.



What do the experts recommend for lumps?




The Society of Surgical Oncology  has come up with practical guidelines (23). In women 35 years of age or younger, all dominant discrete lesions that can be felt on physical examination require referral to a surgeon. If the lump is vague and consists mainly of local thickening, the physical examination should be repeated at the middle of the menstrual cycle after one to two months. If the lump goes away on its own in this situation, the woman is reassured. If the lump persists after one to two months, the patient should be referred to a surgeon. Breast imaging may be appropriate at that time.

All women older than 35 years of age with a dominant mass should undergo diagnostic mammography and, usually, ultrasound as well. Referral to a surgeon is required if the mammogram is abnormal; it is optional, but a good idea even if the mammogram is normal. Post-menopausal women with lumps are referred for surgical consultation after undergoing mammography.

Usual practice to evaluate a breast lump that can be felt is the triple test. This includes palpation, mammography, and biopsy for women more than 35 years of age with dominant masses. When the results of mammographic screening are negative, but a dominant mass is present, biopsy is still required to rule out breast cancer since the  lobular type of cancer may not be visible on mammography.  Among younger women, mammography may be omitted if the results of ultrasound testing and biopsy yield definitive information. 



What do the experts recommend for nipple discharge?




Experts think of  nipple discharge as falling into two categories according to the presence or absence of blood (13). When blood is present, this condition is considered abnormal and absence of blood usually indicates that the discharge is a normal finding.  If no blood is present but the discharge continues for more than one year after stopping nursing or in a women who has not had a child, this is also considered abnormal.  Discharge is considered abnormal if spontaneous (occurring at any time and not just during pressure on the breast).  The presence of a discharge in association with a palpable mass and positive results on mammogram or ultrasound requires evaluation of the mass.  An evaluation for milk in the discharge includes measurement of the milk hormone prolactin and thyrotropin levels. If the levels of both are normal, treatment with dopaminergic agents, such as bromocriptine (Parlodel), may be initiated if the patient desires to reduce the fluid leak.



Prevention of breast cancer




In patients with benign breast lesions that are associated with an increased risk of breast cancer, it is often suggested that they take  tamoxifen or raloxifene as prevention. These agents block the action of estrogen on the breast and have been shown to prevent breast cancer in about half of patients at high risk (24). Current recommendations suggest that women with a five-year risk of breast cancer of more than 1.67% and no contraindications to tamoxifen therapy should be aware of  the option of taking tamoxifen for five years (25). The major factors that increase the risk of breast cancer include a positive family history of breast cancer, early onset of the first menstrual period, late age of first live birth, a history of having breast biopsies in the past, and an older age (typically age 60 and beyond). A recent overview of breast cancer prevention trials showed a reduction of 50% in the relative risk of breast cancer with tamoxifen but the use of tamoxifen can be associated with risks such as blood clots in the legs or lungs, as well as with cancer of the uterus (26) . For this reason, many women at high risk for breast cancer choose not to take these agents.
 

Have you ever wondered how the breast develops at the time of puberty and changes with aging?

 
At the time of puberty, estrogen and progesterone along with substances called growth factors work together to produce the complex treelike structures and the surrounding supporting tissues that make up the breast (Figure 1) (27).  Initially, large ducts called primary ducts are formed, which can be considered to be like the trunks of trees (note that only three are shown in the figure.). From each primary duct, 20-40 smaller (secondary) ducts branch out. These can be considered to be like the major branches of a tree. From these major branches, 10 to 100 sub-segmental ducts form (similar to small branches arising from the large branch of a tree --- note that these are also not shown on the figure). At the end of each of these small branches is a lobe (a group of cells clustered together) consisting of gland cells. The very small ducts with lobules at the end are called terminal end buds. It is these structures which are thought to be the component in which breast cancer develops. In between the ducts and the lobules of glandular tissue are cells that provide a supporting structure and these are called stromal cells. Fat cells are also present in the breast. In adolescent girls, there is very little fat (adipose tissue) in the breast, but as a woman gets older, more and more adipose tissue is present. After menopause, the breast contains predominantly adipose tissue and the lobules and glandular tissues largely disappear in most women. 

In the adult breast, rapid changes occur during the menstrual cycle that result in an increased rate of growth of cells (cell proliferation) during the second half of the month and just before menstrual bleeding .With this increase in cell number, breast size may increase by up to 15%. Later in the cycle, there is an increase in the number of cells undergoing cell death (a process called apoptosis) such that the breast size does not continue to gradually increase over time. At menopause, the numbers of ducts and lobules diminish but overall breast size does not decrease because fats cells replace the areas previously filled with lobules and ducts. 
  


Glossary

 
Adenosis

                                          

When the glandular cells in the breast increase in number together in a small area.

                                                                                                                             

Androgen



A hormone made by men, which causes an increase in facial hair, acne, and body hair – and increases libido or desire for sex. In women, androgens may result in an increase in desire for sex and increased facial hair and acne.



Adipose tissue



The medical term for fat tissue. Adipose tissue consists of fat cells or adipocytes, which are filled with triglyceride, a form of fat.
 
Atypical lobular hyperplasia



This lesion consists of abnormal appearing lobular cells of the breast, which are growing more rapidly than normal This lesion is associated with an increase in risk of breast cancer over time, which is greater than that of lobular hyperplasia. See below



Apoptosis 

           

A normal process by which cells die. In a normal individual, the body completely replaces its cells once every seven years. The cells die by apoptosis and then new cells are formed from those that remain.
 
Anti-estrogen.



A drug that blocks the harmful effects of estrogen on certain tissues like the breast.

 

Atypical ductal hyperplasia



When the cells of the ducts in the breast begin to grow more rapidly, this is called hyperplasia. If the appearance of the cells is abnormal this is called atypical ductal hyperplasia or ADH. This lesion carries with it a high risk of developing breast cancer in the same breast over the following ten years and a high risk for cancer in the opposite breast beyond ten years.



Autopsy

 

When someone dies, a post-mortem examination of the dead body may be performed. This examination is called by the medical term, autopsy.



Axillary Tail
 The axilla is the armpit. When breast tissue grows toward the armpit, the area nearest to the armpit is called by the medical term “axillary tail.”   Blood clots.   Blood cells can form a thickened area, which is called a clot that moves through the blood and can cause damage by blocking blood vessels.  
Bromocriptine (Parlodel)



This is a drug which blocks the production of prolactin and can be used to decrease milk discharge from the breast.



Clinical trial



When physicians want to learn how a medication works, they design a clinical trial in which patients are treated in a certain way.  They closely examine what happens in groups of patients studied and followed over time.  Usually one group is given one drug and a second another drug.  Sometimes the one drug is compared with a sugar pill or placebo.
 
Contraindication.



Medical reasons not to take a medication .



Cooper’s ligament



Tissue in the breast that is like a tendon and acts to support the breast in a post-menopausal woman who have sagging breasts.
 
Costochondritis
 Pain over the joint connecting the rib to the breast bone. This is also called Tsetse’s syndrome. This causes pain which is often interpreted to be breast pain.  
Designer estrogens



These are drugs which have been developed to act as estrogens on some tissues and as estrogen blockers on others.  An example is called raloxifene, which blocks the effects of estrogen on the breast and uterus and acts as an estrogen on the bone.
 
Dominant mass



In women with “lump/bumpy” breast tissue, the dominant mass is larger and more clearly defined than the other rather vague lumps.
 
Ducts



The tube like structures in the breast that carry the milk to the nipple in women who are breast feeding. The ducts sometimes undergo changes leading to localized cancer called ductal carcinoma in situ and to more serious breast cancer called invasive ductal carcinoma.

                                                                                              

Duct ectasia



When the ducts become enlarged in a very localized area.



Ductal carcinoma in situ



Localized cancer of the duct, also called DCIS. This is in contrast to cancer which has invaded the ducts and spread into the tissue.



Estradiol



This is the major female hormone, which is made primarily in the ovaries.



Estrogen.



This is a general term for female hormone. There are three specific female hormones, which are called estradiol, estrone and estriol.  These female hormones cause breast development of young girls and regulation of the monthly menstrual cycle. In the absence of estrogens, several of the symptoms of menopause occur.



Estrone



One of the three female hormones made by the ovary. The estradiol which is made in the ovary can also be converted into estrone in peripheral tissue.



Estriol



A form of estrogen that increases to very high levels during pregnancy, but does not have a major role at times other than pregnancy
  Fibroadenoma  
A type of benign breast lesion commonly found in younger women. It consists of  glandular cells and fibrous tissue. The term fibroadenoma is a combined term referring to the fibrous component ( fibro) and the glandular component (adenoma).



Field Defect or Mutator Phenotype

Field defect  is medical term  that suggests that women with multiple lumps in the breast have some type of underlying defect or abnormality that causes them to be susceptible to multiple abnormalities in the breast. Since many of the multiple lumps contain mutations, a more recent term is mutator phenotype. This refers to a condition where there is a problem which results in more frequent mutations in a tissue. The term phenotype means the physical appearance that results from the mutations that arise in the tissue.



Glandular tissue:



The cells in the breast that respond to estrogen and progesterone and that make milk during the time that a woman is nursing.
 
Hamartoma



Overgrowth of normal tissue in an area. This is a benign condition



Hematoma



A collection of blood under the skin



Histologic



A term for the appearance of tissue when it is cut into very thin sections, stained with a colored dye, and then examined under the microscope.



Hormone



A substance formed in a type of organ in the body called a gland .  The hormone is then carried through the blood to another organ where it acts on that tissue in a specific manner.

Hormone replacement therapy.

This treatment  includes the use of  estrogen plus a progestin.  It can also refer to estrogen replacement alone in women who have had a hysterectomy.

HRT

The abbreviation for hormone replacement therapy

Hypertrophy

When cells in a tissue increase in size, this increases the overall amount of tissue present. The other way that a tissue grows in size is when there are an increased number of cells in the tissue. When the cell size increases, this is called hypertrophy; when cell number is increased, this is called hyperplasia.

Hyperprolactinemia

A condition in which, prolactin, the milk hormone, is increased in the blood.

Intraductal papilloma

Within one of the ducts in the breast there is a growth called a papilloma which is somewhat similar to a wart if examined under the microscope. This may be solitary and if so, is called a solitary papilloma

Lesion

This is the medial term to describe an abnormal piece of tissue in the body. A lesion can be a benign lump, a cancer, or merely something such as a mole on the skin.

Lipoma

Localized overgrowth of fat or adipose cells. This is felt to be a benign tumor.

Lobular carcinoma in situ

This is a more advanced form of atypical lobular hyperplasia. Even though this is called carcinoma in situ, most experts feel that this lesion is not a form of cancer, but an advanced pre-malignant lesion.

Menopause.

Time of life when the ovaries stop making estrogen and the monthly menstrual periods   stop.   Change of life is another way to describe the menopause.

Menstrual

Refers to the process of menstruation (see below)

Menstrual cycle

The monthly cycle during which a woman bleeds once per month.

Menstruation

When female hormone levels fall during the monthly cycle, the lining of the uterus is  shed and  bleeding occurs  through the vagina.  Some call this a “monthly” or a monthly period.

Multifocal

This refers to the fact that certain lesions in the breast are found in several locations and not just one.  The word multifocal means the lumps or other lesions are found in several different places in either the  same breast or in the opposite breast.

Mutations

The genes in the body consist of a biochemical substance called DNA. When there are small changes in DNA this causes abnormalities in the function of proteins and other body chemicals. The DNA changes are called mutations.

NSAIDs

These are drugs such as ibuprofen (Motrin) or naproxen (Aleve), which are used to reduce pain. NSAID is an abbreviation for non-steroidal anti-inflammatory drugs.

Neurofibroma

A benign tumor consisting of nerve fiber tissue from the nervous system.

Non-sclerosing adenosis

An increase in local areas of gland tissue without scar tissue present.



Observational study

In this type of study, groups of patients who are already receiving certain therapies are carefully observed to see the safety and effectiveness of one therapy compared to another.  Because there's no random selection procedure, bias may influence the results and sometimes this type of study gives results that are incorrect.  Randomized trials are much more accurate means of testing the safety and efficacy of drugs.

Ovary

One of a pair of female glands that produce eggs and the female hormones, estrogen and progesterone.  The ovary also produces male type hormones called androgens.

Papillomatosis

           

The presence of multiple wart like lesions that are growing in a breast duct

.

Periductal  fibrosis

Scarring in the tissues just outside of, but very near to the duct

Prolactin

A hormone made by the pituitary gland that controls milk production at the time of breast feeding and if elevated at another time can be associated with persistent milk discharge which in medical terminology is called galactorrhea.

Radial Scar 

A lesion  in the breast that appears to have scar tissue in it in a spoke-like pattern.

                                                                                       

Pituitary
  The gland that sits in the lower part of the skull just above the sinuses in the nose. It is often called the master gland because the pituitary controls growth via growth hormone, milk production via prolactin, and the thyroid, adrenals and reproductive glands including the ovaries in women and testicles in men.
Placebo

During a clinical trial, one group of patients is often given a “dummy pill” that looks similar to the pill used in the trial. A common term for “placebo” is “sugar pill”.

Premenstrual syndrome

Symptoms of anxiety, altered mood and decreased energy that occur during the last week before the onset of menses. It usually resolves during the first two to three days after the start of menses.

Post-menopausal

Describes the time after menopause when the monthly menstrual periods stop and the ovaries no longer make estrogen. This condition usually continues for the remainder of a woman’s life. In rare instances, a few menstrual cycles return, even after they have stopped for more than one year. This is the reason that some women are said to have “menopausal babies.”

Pre-menopausal

Describes a  time of life when a woman gets monthly periods and her reproductive function is normal. The average age of menopause is 51 in non-smokers and 49 in smokers.

Progesterone

A female hormone that acts on the uterus (womb) to prepare for receiving an egg  following fertilization by a sperm from a male partner. The drop in  progesterone levels each month causes the bleeding associated with menstrual period.

Progestin

This is a synthetic form of progesterone. This class of drugs was originally developed   for use in birth control pills. These hormones work very similarly to natural progesterone on the body.

Randomized trial.

A type of clinical trial in which two or more types of treatment or one treatment and a sugar pill (placebo) are compared. The purpose of a randomized trial is to eliminate bias and to learn how the treatments affect groups of patients. A randomization process is used to tell patients which therapy they will receive. That decision is not made by the researchers running the study, but by a coin toss or similar computer technique. The advantage of a randomized trial is that the groups being treated usually have similar ages, ethnic backgrounds, and risk factors. The outcomes being studied (for example the number of heart attacks) are primarily determined by the treatments themselves and not other factors. The randomized clinical trial is thought to be the most accurate way of finding out information about hormone or other therapy and is the least susceptible to potential bias.

Radicular pain

This is a type of pain that comes from a pinched nerve, such as in the neck, which causes a sharp, knife-like pain in the area which the nerve serves. Women can perceive a pinched nerve in the neck as pain in the breast.

Raloxifene

An anti-estrogen that blocks the effect of estrogen on the breast, but acts as an estrogen on bone. This medication can be used to prevent breast cancer and has been used to treat loss of bone.

Sclerosing adenosis

An area of increased glandular tissue in a localized area associated with scarring.
 
Society for Surgical Oncology

The professional organization for surgeons and their non-physician health care providers  who are involved in the care of patients who usually undergo  operations  for breast lumps and breast cancer .

Stromal cells

Cells in the breast located between the ducts and the glandular tissue that provide support for these structures.

Tamoxifen

A commonly used anti-estrogen that blocks the effect of estrogen on the breast. This drug is commonly used for the treatment of breast cancer and less commonly for the prevention of breast cancer.

Traumatic



This refers to major physical insults to the body such as a fall from a high place, an automobile accident, an object falling on you, or a physical beating. Trauma can often be severe enough to result in death. Under those circumstances, an examination of the dead body, called an autopsy, is usually preformed. The breast can then be examined under the microscope at that time and lesions detected that would not otherwise have been found.  

Tsetse’s syndrome

Pain over the joint between the rib and the breast. This causes pain over this area which is often interpreted by the patient to be breast pain.

Typical lobular hyperplasia

This lesion consists of normal appearing lobular cells of the breast, which are growing more rapidly than normal. This lesion is associated with a slight increase in risk of breast cancer over time.

SERM

This is an acronym for selective estrogen receptor modulator. Others call this class of drugs “designer estrogens.”  These agents act like estrogens on some tissues, such as bone but anti-estrogens on other tissues  such as breast. With the right combination of actions, these drugs could potentially increase the benefit of estrogens without increasing their harmful effects or side effects. At the present time, SERMs such as raloxifene are available and others are in development. No SERM can yet do exactly all of the things that are necessary to eliminate their side effects but, in time, such agents might become available.

Unfolded lobules

When the small ducts and glands at the ends of them (terminal end buds) enlarge, they become dilated and unfold. This is a technical name given to these structures when they begin enlarging.
 
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