~Fibrocystic Breast Disease

~Fibrocystic Breast Disease
Reprinted with permission of Life Extension®.
  • Normal Breast Tissue
  • Nodules With Potential For Cancer
  • Risk Factors Of Breast Cancer
  • Hormone Replacement And Breast Cancer
  • Other Causes
  • Diagnosis
  • Treatment
  • Hormone And Drug Therapy
  • Nutritional Recommendations
  • Other Considerations
  • Summary


Breast nodules are a frequently presented gynecologic complaint. These nodules have two chief causes: benign breast disease and cancer. However, benign breast disease is the most common cause of nodules and can stem from cyst formation, obstructed ducts, inflammation, or infection. Although benign breast nodules have several causes and manifest themselves differently, for purposes of this discussion, all fibrous nodules or lumps will be referred to as fibrocystic breast disease (FBD).

According to the National Cancer Institute/National Institutes of Health (2001a,b), fibrocystic breast disease (FBD) is a common condition that affects many women at some time in their lives. FBD is most common between the ages of 30 and 50 (AMA 1989), but younger women as well as menopausal women taking hormone replacement therapy (HRT) may also experience FBD (Imaginis 2000). More recently, some physicians have preferred to call FBD, fibrocystic breast "condition" or "change" (FBC).

The symptoms of FBD can vary significantly. Some women experience severe breast tenderness and pain with multiple lumps in both breasts. Other women have only mild tenderness with no detectable lumps. In some women the symptoms are relatively constant, while in others the symptoms come and go either monthly or over several months. According to the National Cancer Institute (2001a), the chances of developing FBD are greater in women who have never had children, women who have irregular menstrual cycles, or women who have a family history of FBD or breast cancer.

FBD is a condition generally characterized by lumps that move freely in the breast tissue and vary in texture and size (Lark 1996). However, because the clinical signs of breast cancer are not easily distinguished from benign breast conditions, all breast lumps should be examined by a physician and not be assumed to be benign. Only a physician can determine the nature of breast lumps or changes (National Cancer Institute 2001a).

Because FBD is a benign condition, it usually does not lead to breast cancer (American Cancer Society 1991, 1997; National Cancer Institute 2001b). Fortunately, only about 5% of FBD cases involve the type of changes that would be considered a risk factor for developing breast cancer. However, benign conditions may eventually result in calcifications (Anon. 1998). Calcifications are quite small--sometimes as small as a grain of salt--and cannot be detected during a routine exam; however, calcifications may be detected by routine mammography. Since calcifications may be associated with some types of pre-malignant lesions, it is important to follow your physician's recommendations concerning the frequency of mammography (AMA 1989).

NORMAL BREAST TISSUE
  • Breast Nodules
  • Benign Nodules


The breast is composed of 15-20 lobes of milk-secreting glands that are embedded in fatty tissue. Ducts link the lobes of these glands and have an outlet through the nipple. The area between the lobules and ducts is filled with fatty tissue. Breast tissue itself contains no muscles; however, there are small, very fine ligaments throughout the breast that attach to the skin and determine the shape of the breast. There are no muscles in the breast itself, although pectoral muscles lie just under each breast and over the ribs (AMA 1989).

The breasts undergo changes each month when a female begins to have menstrual periods. Hormones that are implicated in development of breast mammary glands and worsening premenstrual breast symptoms are estrogen and progesterone, the main female hormones, and prolactin, the milk release hormone secreted by the pituitary gland (Lark 1996). An increase in prolactin may also be responsible for some FBC changes because higher levels of p rolactin seem to be connected with a higher occurrence of FBC. (Prolactin levels of over 100 ng/mL may be a causative factor). Often the painful symptoms of FBD will decrease once menstruation begins. In some women, however, the repeated cycles of hormonal stimulation result in chronic inflammation and development of fibrous tissue. When fibrous tissue makes it more difficult for the fluid in breast cysts to escape and be normally absorbed by a woman's body, the cysts become denser, which can cause pain and pressure on surrounding tissues (Lark 1996). This fibrous tissue is similar to the type of tissue in ligaments and scars and feels firm, thick, rubbery, and ridge-like. It may also feel like small or large beads scattered throughout the breast.

In addition to estrogen, progesterone, and prolactin, all naturally occurring female hormones, many other natural hormones (hypothalamic, other pituitary hormones, thyroid, parathyroid, adrenal, pineal, pancreas, ovarian, and duodenal hormones) can also contribute to FBD (Ayers 1983; AMA 1989). Environmental estrogens, called xenoestrogens, may also contribute to human hormone levels. Xenoestrogens come from phytoestrogens (produced by plants), dietary estrogens from meat and dairy products, and many other chemicals such as pesticides, fertilizers, alklyphenols (used in detergents), and plastics (food packaging) (Nimrod et al. 1996). Additionally, as women approach menopause, they have an additional, complicated decision to make concerning the use of synthetic hormone replacement therapy (HRT) (Lundstrom et al. 2001; Mayo Clinic 2001; Women's Health Initiative Investigators 2002).

Breast Nodules

As stated earlier, because breast tissue is naturally a glandular type of tissue, almost all women develop nodules or lumps in their breasts at some time or another. Lumps, also called "dominant lumps," feel different from surrounding tissue (AMA 1989). Some may be quite large, while others are small and even diffuse over time (Lark 1996). Fibrous tissue in the breast may even be mistaken for a lump. Breast nodules or lumps are the result of several medical causes, including cysts, fibroadenomas, areolar gland abscesses, breast abscesses, intraductal papillomas, mammary duct ectasia, mastitis, Paget's disease, and cancer (Anon. 2000).

Benign Nodules
  • Cysts * Sclerosing Adenosis * Intraductal Papillomas


Cysts

Cysts are the most common cause of nodules or breast lumps. Cysts are usually smooth, round, fluid-filled, and slightly elastic. Although the fluid that comes from a cyst is often discolored, the color of the fluid is of little cause for concern unless it is bloody. Cysts occur as an isolated lump, in clusters, or widespread with well-defined lumps of various sizes. Cystic lumps are mobile and do not attach themselves to underlying breast tissue; therefore, cysts do not produce tissue deviation or dimpling. Mobility is one major characteristic that differentiates cysts from malignant nodules. However, cysts are sometimes accompanied by thickened adjacent tissue that is palpable and not so mobile. Breast cysts may also produce a discharge from the nipple that varies from clear and watery to sticky (AMA 1989).

Cysts frequently occur in the upper outer quadrant and the underside of the breast. Symptoms range from a feeling of fullness or heaviness to a dull ache, extreme sensitivity, or a burning sensation. For some women, these symptoms may be severe, making exercising or sleeping on their stomachs painful.

Cysts also often increase in size and tenderness in response to the monthly menstrual cycle because breast tissue undergoes changes related to the normal rise and fall of hormone levels (Lark 1996). After menstruation, the changes and symptoms sometimes abate. Physicians recommend that the best time for breast examination is about 7-10 days after the start of menstruation when breast tissue is more likely to be at its most normal state. Sometimes, after menopause, FBD symptoms completely disappear or become less noticeable (without HRT) (Imaginis 2000).

The occurrence of multiple cysts in one or both breasts is also common in FBD (also called fibroadenosis or chronic cystic mastitis) (Anon. 2000). If a mass is determined to be a cyst, the next step is to determine if it is a simple cyst (one compartment) or a complex cyst (more than one compartment within the cyst). Simple cysts are very unlikely to be malignant.

Sclerosing Adenosis

A benign condition with excessive tissue growth in the lobules of the breast is sclerosing adenosis (National Cancer Institute 2001b). The condition frequently causes breast pain. Sclerosing adenosis may produce lumps and appears on a mammogram as a calcification (a small deposit of calcium) in breast tissue.

Intraductal Papillomas

Small, wart-like, benign growths that project into the breast ducts near the nipple are intraductal papillomas (National Cancer Institute 2001b). They usually occur singly, but can also appear as multiple lesions. The smaller nodules are difficult to palpate. The primary sign of intraductal papilloma is nipple discharge, either clear or bloody. Breast pain and tenderness may occur.

NODULES WITH POTENTIAL FOR CANCER
  • Complex Cysts
  • Fibroadenomas
  • Paget's Disease
  • Phyllodes Tumor


Complex Cysts

Complex cysts have more than one compartment within the cyst. Ultrasonography is valuable in differentiating simple cysts from complex cysts or solid masses (Bassett et al. 1991). Complex cysts are somewhat more likely to be cancerous, so doctors will often order further tests, beginning with fine needle aspiration and perhaps a biopsy, to be certain the cyst is not cancerous or pre-cancerous.

Fibroadenomas

Fibroadenomas (sometimes called adenofibromas) are smooth, firm, benign tumors that are extremely mobile, feel slippery, and move around easily in the breast. They consist of structural (fibro) and glandular (adenoma) tissue (Anon. 2000, National Cancer Institute 2001b). Fibroadenomas feel round with well-defined margins and vary from pinhead in size to very large. They grow rapidly and usually occur near the nipple or on the outside of the upper quadrant. Fibroadenomas occur most often in women in their 20s and 30s and occur twice as often in African-American women as in other American women (National Cancer Institute 2001b). When aspirated, if there is no fluid in the lump, it is most likely a fibroadenoma. Fibroadenomas do not cause pain or tenderness. A "complex" fibroadenoma contains abnormal growths or exhibits abnormal cell changes. Although fibroadenomas themselves do not become cancerous (National Cancer Institute 2001b), they can act as markers for the disease. Women with a family history of breast cancer who also develop complex fibroadenomas might be at a higher risk for developing cancer than other women. Fibroadenomas are not difficult to remove and rarely recur.

Paget's Disease

A slow-growing intraductal carcinoma that begins as a scaling, eczema-like lesion on the nipple is called Paget's disease (Anon. 2000). The nipple becomes red and irritated and the lesion extends along the skin and into the ducts. The lesion can progress to a mass located deep in the breast.

Phyllodes Tumor

Phyllodes tumor is a breast tumor that might be malignant (Mazy et al. 1999). Phyllodes tumor is a rare type of breast tumor, similar to a fibroadenoma, but it is composed of an overgrowth of fibrous connective breast tissue that can become quite large. If malignancy is discovered (rare) through biopsy, the tumor and a margin of normal breast tissue are removed surgically.

FACTORS AFFECTING INCREASED RISK OF BREAST CANCER

When a woman finds a breast nodule, the first concern is that it might be cancerous. Most of the time, breast nodules are not cancerous (benign). According to Hurley et al. (1997), there are three basic, agreed-upon classifications of benign breast disease: nonproliferative, proliferative without atypia, and atypical hyperplasia. However, there can be an association with benign changes in the breast in young women and an increased risk of breast cancer with age, particularly later in life. Therefore, pathologists sometimes add comments to the pathology report indicating whether or not benign changes are relevant to an increased risk of cancer. One study followed 644 women with breast nodules between 1976 and 1982. The researchers found a relationship between subsequent cancer in women with multiple cysts and in 15 of the women whose cysts had been aspirated. The authors concluded that women with multiple breast cysts that have been aspirated have an increased risk of breast cancer. These women should perform more breast self-examinations and have follow-ups accordingly (Bundred et al. 1991).

Benign breast conditions are more often found in premenopausal women (Ernster 1981; Bodian 1993a). Breast cancer occurs more often in postmenopausal women (75% of cases) (NBCC 1999). Estimating the risk for future breast cancer from a benign condition is difficult: the extent of mammography screening differs in the population and often, significant time passes between diagnosis of benign disease in a younger woman and the increased risk for breast cancer development in older women. Because benign breast disease is difficult to distinguish from malignant disease, diagnostic biopsy is required for a definitive diagnosis (NBCC 1999).

Women with biopsy-confirmed benign disease do appear to have an overall modest increase in risk for subsequent development of breast cancer, particularly for more hyperplastic or epithelial (the covering or lining) proliferative forms. However, the evidence regarding the risk of breast cancer for nonproliferative conditions is conflicting. Some research found that the risk of breast cancer for women with nonproliferative disease is about double that of women without benign disease (Bodian et al. 1993b), while others find that lesions with no proliferative changes were not associated with an increased risk (Oza et al. 1993; Henderson et al. 1996; NBCC 1999). According to Hurley et al. (1997) atypical hyperplasia is a risk factor, but it is not with certainty followed by breast cancer; risk applies to both breasts, with greater risk on the affected side. There is no means to predict which women will go on to develop breast cancer and the effectiveness of current screening and management methods is unknown. Further complicating a physician's ability to predict a woman's risk for breast cancer is that most women do not have a history of biopsy for a benign lesion. Additionally, at the time of this writing there is no generally agreed upon classification of mammography patterns of breast tissue that is a predictive measure of which conditions are indicative of increased risk (Bodian et al. 1993c; NBCC 1999).

Hormone Replacement and Breast Cancer
  • Signs of Breast Cancer
In the July 17, 2002 edition of the Journal of the American Medical Association, after decades of accumulated observational evidence, the Women's Health Initiative Investigators group raised concerns about the balance of risks and benefits for hormone use in healthy postmenopausal women. The concerns resulted from a randomized controlled primary prevention trial. The trial recruited 16,608 postmenopausal women (50-79 years of age) with an intact uterus at age 40 to United States clinical centers from 1993-1998. The study was designed to last 8.5 years. Participants in the study received placebo (8102 subjects) or conjugated equine estrogen (0.625 mg daily) plus medroxyprogesterone acetate (2.5 mg daily) in a single tablet (8506 subjects), commonly known as Prempro. The study monitored coronary heart disease, invasive breast cancer, stroke, pulmonary embolism, endometrial cancer, colorectal cancer, hip fracture, and death due to other causes.

After 5.2 years, the data and safety monitoring board recommended stopping the trial because one statistic (for invasive breast cancer) had exceeded the stopping boundary for an adverse effect and the global index statistic supported risks exceeding benefits. Although the absolute risk was still low, investigators stopped the estrogen plus progestin part of the study. They concluded: "Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal U.S. women." Women in the other groups in the study (women taking estrogen alone, on a low-fat diet, taking calcium and vitamin D supplements, and women in the observation-only group) were advised to continue with their assigned treatment regime. However, prescribing the combination of estrogen and progestin was not recommended for long-term use or for prevention of chronic diseases (Women's Health Initiative Investigators 2002). Theories abound about why there appear to be complications with combination HRT, with one being that the progestin part of the therapy may have an antagonistic action on the estrogen part. Other co-factors include obesity, diabetes, and influence of family health history.

Another much smaller study in 2001 (158 women: 58 using HRT with Prempro (conjugated equine estrogen, 0.625 mg, plus medroxyprogesterone acetate, 5 mg); 51 using low-dose oral estrogen alone (estriol), 2 mg daily; and 55 using transdermal estrogen via a patch with estradiol, 50 mcg each 24 hours) evaluated the impact of different HRT regimens on mammographic breast density. Independent radiologists were unaware of the HRT and analyzed coded mammography films. The research indicated that an increase in mammographic density was more common in women taking continuous combined HRT (40%) than in those using oral low-dose estrogen (6%) or transdermal (2%) treatment (Lundstrom et al. 2001). The researchers reported that increased density was already apparent at the first visit after beginning HRT. During long-term follow-up, there was very little change in mammographic status, leading Lundstrom et al. (2001) to conclude that there was an "urgent need to clarify the biological nature and significance of a change in mammographic density during treatment and, in particular, its relation to symptoms and breast cancer risk."

Scientists, environmentalists, physicians, and governmental agencies have all produced reports in support of their particular stance on hormones: are they safe or not and should they be used or not? Therefore, in light of continuing concerns about the safety of using HRT, particularly HRT containing estrogen plus a progestin component, decisions concerning hormone use and modulation are personal ones related to each woman's particular risk factors and her reasons to consider using HRT. It is more important than ever to consult your physician for guidance concerning the decision to use any hormone therapy (also see the Female Hormone Modulation Therapy protocol).

Signs of Breast Cancer

Nodules that are hard, poorly delineated, and fixed to the skin or to underlying tissue are suggestive of breast cancer. Cancerous nodules can cause dimpling, nipple deviation, or nipple retraction. They usually occur singly and often are not painful. There may be nipple discharge that is clear or bloody. Bloody discharge is more suggestive of breast cancer. Ulceration may occur in later stages (Anon. 2000). (Further discussion of breast cancer is beyond the scope of this protocol. See the Breast Cancer protocol for a discussion of additional information.)

OTHER CAUSES OF BREAST NODULES
  • Mammary Duct Ectasia
  • Pseudolumps
  • Fat Necrosis
  • Breast Pain
Mastitis or postpartum mastitis is an infection in women who are breastfeeding in which a milk duct becomes blocked, causing milk to pool, permitting a bacterial infection, and resulting in inflammation (AMA 1989). The breast appears red and feels warm and may also be tender. Mastitis can be accompanied by chills, fever, and cracking of the nipple.

Mammary Duct Ectasia

Mammary duct ectasia causes ducts beneath the nipple to become clogged and inflamed, particularly in women nearing menopause or in postmenopausal women (National Cancer Institute 2001b). The condition can be itchy and tender, with transient pain, and it may produce a thick, sticky multicolored discharge. The skin over the nodule may even be a blue-green color. Nearby lymph nodes can also be inflamed.

Pseudolumps

Pseudolumps are normal lumpy areas of breast tissue. This type of lumpiness will often disappear or vary with cyclic hormonal levels. Pseudolumps also result from silicone injections to enlarge the breasts or as a consequence of breast surgery or radiation therapy.

Fat Necrosis

Fat necrosis produces painless, round, firm lumps that form from damaged and disintegrating fatty tissue (National Cancer Institute 2001b). Fat necrosis is more likely to occur in obese women with large breasts. It may also develop in response to a bruise or blow to the breast. Sometimes the skin around these lumps looks red or bruised.

Breast Pain

Mastalgia refers to breast pain that is severe enough to cause a woman to seek medical treatment. Mastalgia can occur at rest or during movement, intermittently, cyclically, or constantly and can be sharp or dull and radiate to the back, arms, or neck. Pain can be aggravated by palpation (such as during physical examination). However, mastalgia is an unreliable indicator of a serious condition such as cancer (Anon. 2000). Although many women experience uncomfortable tenderness and swelling, pain characterized as severe occurs only about 15% of the time.

Breast pain not related to the menstrual cycle is called non-cyclical breast pain. Non-cyclical breast pain is rare and much more difficult to treat. Non-cyclical breast pain can be caused by old trauma to the breast (such as a blow to the breast, a biopsy, or surgery), infection, or some other condition completely unrelated to the breast (Anon. 2000). Arthritis is a possible cause of breast pain. Arthritis pain is usually felt in the breastbone, at the center of the chest. Women with arthritic breast pain also may experience increased discomfort when they breathe deeply.

An early study showed that there were significant abnormalities in pituitary function (via prolactin mechanisms) seen in severe cyclical mastalgia and nodular breast disease, but not in women with noncyclical mastalgia (Kumar et al. 1984).

DIAGNOSING FIBROCYSTIC BREAST DISEASE

A healthcare provider who is experienced in diagnosing breast conditions should examine any new breast mass or lump. Additionally, if there is any skin irritation, dimpling, nipple pain or retraction, redness or scaling of the nipple or breast skin, or nipple discharge other than breast milk in lactating women, see a physician for an evaluation. Breast conditions usually can be diagnosed by an examination by a physician. It is not unusual for a physician to recommend a mammogram, ultrasound, or biopsy procedure to assist or confirm the diagnosis (National Cancer Institute 2000b).

A mammogram, the most frequently used diagnostic tool for breast lumps, is a type of x-ray examination. If the mammogram suggests that abnormal tissue is benign, follow the physician's recommendations and recheck the lump (in perhaps 4 to 6 months) (National Cancer Institute 2000b). If the mammogram is inconclusive or if it indicates the need for further examination, your physician may recommend a computer-aided diagnosis procedure using ultrasound. This additional diagnostic procedure is designed to improve identification of a potentially malignant lesion.

Ultrasound uses high-frequency waves to outline a part of the body and is useful to further evaluate possible abnormalities found during mammograms or physical examinations. Besides aspiration, ultrasound is the only way to determine if the lump is a fluid-filled cyst. Fluid-filled cysts have a distinctive appearance on an ultrasound screen.

Fine-needle aspiration biopsy (FNAB) is used if the physician is almost certain that the lump is a cyst. Aspiration is also used to extract a material from a lump for further analysis (National Cancer Institute 2001b). A very thin needle is inserted into the breast tissue as the doctor palpates the lump. The procedure is essentially painless because nerves are located primarily in the skin, not in the breast tissue itself. Ultrasound is used to guide the needle when a lump is difficult to palpate or is very small. FNAB has decreased the need for surgical biopsy.

Core-needle biopsy uses a needle larger than the type employed with FNAB. The procedure is performed in a physician's office with local anesthesia of the breast area to be biopsied. Core-needle biopsy removes a small cylinder of tissue for examination.

Stereotactic biopsy is a newer approach that relies on a three-dimensional x-ray to guide the needle biopsy of non-palpable mass (National Cancer Institute 2001b). The breast is x-rayed from two different angles and a computer plots the position of the suspicious area. Once the area is precisely identified, the radiologist uses a needle to biopsy the lesion.

Surgical biopsy may also be necessary to remove all or part of a lump for examination (National Cancer Institute 2001b). This procedure is done either in a physician's office or in an outpatient hospital facility under intravenous sedation or local anesthesia.

There are newer methods, such as vacuum-assisted biopsy, which remove even more tissue, but so far there is no universal agreement about when these procedures should be used, even though current studies show consistent reliable results (Fine 2001; Maganini et al. 2001; Ohsumi et al. 2001; Jackman et al. 2002; Perlet et al. 2002).

Continued . . .


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