Fibrocystic breast changes are non-cancerous lumps or abnormalities in the breast tissue. Between 50% and 90% of women will experience benign changes in their breast tissue during their lifetime, with 30s and 40s being the most common age of occurrence.

It is important for women who notice changes in their breast tissue to let their doctor know right away so that breast cancer or another serious disease can be ruled out.
Symptoms of fibrocystic breast changes include:

• Tenderness in both breasts
• Sense of fullness
• Pain that is generally worse before the menstrual period and relieved within a few days of the onset of the menstrual period
• Breast lumps that are tender, can be moved easily, may be present symmetrically in both breasts, and may change in size with the menstrual cycle
• Nipple discharge may occur in up to 15% of women

Natural interventions that can help ease symptoms and reduce incidence include vitamin E, plant lignans, and chasteberry (also known as Vitex agnus-castus).

Risk Factors:

Several risk factors promote fibrocystic breast changes:

• Peak occurrence in 30s and 40s
• Alcohol intake during adolescence and early adulthood

Diagnosis:

Certain tests beyond breast self-exam, clinical exam or mammography may be necessary to distinguish benign breast changes from breast cancer:

• Ultrasound
• Breast biopsy, including fine needle aspiration, core needle biopsy, image-guided biopsy, or surgical biopsy
• Near-infrared imaging with contrast since cancerous breast tissue is more likely to absorb contrast media than benign breast tissue

Conventional Medical Treatments:

Drugs that may address the symptoms of fibrocystic breast changes include:

• Non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen
• Medications that influence hormones, including oral contraceptives, cabergoline, tamoxifen, and danazol
• Ormeloxifene, currently used as an oral contraceptive primarily in India

Dietary and Lifestyle Changes:

• Dietary fiber for improved estrogen metabolism
• Increased fruit and vegetable intake; higher citrus fruit consumption was associated with 57% reduced odds, and higher fruit (other than citrus) with 65% reduced odds
• A fiber-rich, plant-based diet high in healthy fats from sources such as olive oil and fish, and low in red meat

Integrative Interventions:

• Chasteberry: Chasteberry, also known as Vitex agnus-castus, is commonly used for breast pain, especially premenstrual breast tenderness.
• Plant lignans: Lignans are compounds present in a variety of plant foods, with high concentrations found in flaxseeds and sesame seeds, as well as in certain plant extracts such as Norway spruce. Women who consumed the most food sources of lignans were 52% less likely to have benign breast changes than those with the lowest consumption of these foods.
• Vitamin E: Vitamin E was shown to be effective in reducing the most severe premenstrual breast pain in a clinical trial.
• Evening primose oil/gamma-linolenic acid (GLA): Evening primrose oil, which contains GLA, was found to reduce the most severe premenstrual breast pain when taken at a daily dose of 3 g for six months.
• Omega-3 fatty acids: Breast pain intensity was reduced by about 42% in women given omega-3 fatty acids after two menstrual cycles, while women who did not receive the omega-3 supplement experienced a reduction of only about 17%.

Fibrocystic breast changes are non-cancerous (benign) lumps or abnormalities in the breast tissue. Fibrocystic breasts are very common: estimates suggest that between 50% and 90% of all women will experience benign changes in their breast tissue during their lifetime (Jones 2011). In fact, most doctors no longer use the term "fibrocystic breast disease" because the condition typically does not require urgent action (Alvero 2015; Jones 2011; Mayo Clinic 2013a).

Some types of fibrocystic breast changes are associated with a small increase in breast cancer risk, particularly when there is a family history of breast cancer. However, fibrocystic changes are often not associated with an increased risk of breast cancer (Tamimi 2010; Sugg 2014; Guray 2006). Importantly, women who do notice changes in their breast tissue should let their doctor know right away so breast cancer or another serious disease can be ruled out (Jones 2011; Alvero 2015).

Physicians typically use imaging tests followed by biopsy studies to evaluate breast masses for the presence of cancer. If changes in a woman's breast tissue are determined to be benign and do not cause symptoms, then no treatment is necessary. If breast changes cause mild-to-moderate pain or discomfort, then over-the-counter pain relievers such as acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) may help, but these drugs are not without side effects (ACR 2012). For women whose symptoms are more severe, drugs that alter hormonal activity may be used to relieve pain, but these may have side effects (Alvero 2015; Jones 2011; Sugg 2014). Less commonly, symptomatic breast changes may be due to an infection, in which case antibiotics can be used (Jones 2011).

Fortunately, there are several actions women can take on their own that may help ease symptoms caused by fibrocystic breast changes and reduce the incidence of these conditions. For example, increasing intake of dietary fiber is believed to decrease the incidence of benign breast conditions (Jones 2011). Several natural interventions may also be of benefit, including vitamin E, omega-3 fatty acids, plant lignans, and chasteberry (also known as Vitex agnus-castus) (Vaziri 2014; Jones 2011; Altern Med Rev 2009).

Hormonal imbalances are generally thought to underlie fibrocystic breast changes. Specifically, estrogen excess, inadequate progesterone, or abnormal metabolism of these hormones appear to contribute to benign changes in breast tissue (Jones 2011). Given the important role of hormones in fibrocystic breast changes, women are also encouraged to read the Female Hormone Restoration protocol.

Structure and Function of the Breast

Breast tissue is composed of ducts, lobules, ligaments, connective tissue, blood and lymphatic vessels, lymph nodes, nerves, and fat (Mayo Clinic 2015a). Each female breast contains 10–15 ducts that begin within the breast and merge at the nipple. It is through these ducts that milk passes during lactation. For each duct, there is a lobule surrounded by fat cells. The lobule is the milk-producing structure in the breast (Johns Hopkins Medicine 2012; Neville 2014). The breast is supported by ligaments and bands of fibrous tissue that together determine the breast's shape and position (Prendergast 2013).

Breast lobules and ducts react to hormones to produce milk during lactation. The pituitary gland at the base of the brain releases prolactin and oxytocin, which stimulate milk production and release (Nussey 2001). However, breast tissue is also responsive to estrogen and progesterone (Mauvais-Jarvis 1986). All four of these hormones are important for the appropriate timing of lactation, suppressing ovulation during lactation, milk production and expression, and growth and maturation of breasts during development (Clevenger 1997; Jonas 2009; Bellmann 1976; Neville 2009).

Types of Fibrocystic Breast Abnormalities

Benign breast conditions are divided into three categories based on how the tissue extracted during a biopsy looks under a microscope (ie, histologically) (Dupont 1985; Tamimi 2010; Mayo Clinic 2013b; ACS 2015). The categories are:

• Non-proliferative (no increase in cell number or growth)
• Proliferative without atypia (overgrowth of normal-appearing cells lining breast lobules and ducts)
• Atypical hyperplasia (overgrowth of abnormal-appearing cells lining breast lobules and ducts)

These categories indicate risk of the abnormality becoming breast cancer (Schnitt 2003; Hartmann 2005; Dupont 1985; Guray 2006):

• Women with non-proliferative changes generally do not have increased breast cancer risk.
• Women whose benign breast abnormalities are proliferative without atypia have a 1.3- to 2-fold increased risk of breast cancer compared with women who have non-proliferative benign breast disorders.
• Women with atypical hyperplasia have a 4- to 13-fold increased risk of breast cancer compared with women who have non-proliferative changes.
• There are two types of atypical hyperplasia: ductal and lobular.

Table 1: Types of Benign Breast Disease

Other Breast Abnormalities

A variety of other breast abnormalities may cause signs and symptoms similar to those caused by fibrocystic changes.

Table 2: Other Breast Abnormalities that may Resemble Fibrocystic Changes

The Cause of Fibrocystic Changes

The precise cause of fibrocystic changes is not known, but hormonal imbalances are strongly implicated as a contributing factor (Alvero 2015; Jones 2011). A relative deficiency of progesterone or excess of estrogen during the luteal phase of the menstrual cycle may lead to fibrocystic changes (Vorherr 1986; Horner 2000; Carbonaro 2012). The luteal phase occurs after ovulation, when an egg is released by an ovary; this phase lasts until the onset of the menstrual period. The luteal phase usually lasts 14 days (UCSF 2015). During the luteal phase, breast tissue may become tender and lumps may increase in size (Cleveland Clinic 2014).

Fibroadenomas, which are a type of fibrocystic change composed of fibrous and glandular tissue, are particularly sensitive to hormonal changes (Yu 2013; Greenberg 1998). In fact, these breast abnormalities can produce milk during pregnancy and they recede beginning in perimenopause as hormone levels decline. Therefore, women may be more likely to experience symptoms caused by a fibroadenoma during pregnancy and lactation (Yu 2013). Also, women who begin oral contraceptives before age 20 have an increased risk of developing fibroadenomas (Yu 1992; Estevao 2007; Guray 2006).

Age

The incidence of benign breast abnormalities peak in women's 30s and 40s (Sugg 2014). This is in contrast to risk of breast cancer, which continues to increase after menopause (Guray 2006).

Alcohol Consumption

Alcohol intake during adolescence and early adulthood increases risk of proliferative benign breast conditions (Liu 2012; Berkey 2010).

Caffeine and Related Compounds

At one time, it was believed that methylxanthines—a class of naturally occurring stimulant molecules that includes caffeine and theobromine, a compound in cacao—aggravated symptoms of fibrocystic breasts, or caused fibrocystic abnormalities to increase in size. However, a rigorous analysis of studies on the subject failed to show a beneficial effect of methylxanthine avoidance on fibrocystic changes (Franco 2013; Horner 2000). Avoidance of methylxanthines is still sometimes recommended, but the benefit for women with fibrocystic changes is uncertain (Jones 2011; Alvero 2015; Sugg 2014).

Fibrocystic changes occur in at least half of women and are uncommonly associated with the development of breast cancer. However, the primary importance of diagnosing benign breast disease is to rule out more serious conditions, including breast cancer (Sugg 2014; Alvero 2015; Jones 2011; Vaidyanathan 2002).

Unfortunately, benign breast conditions are often misdiagnosed since each woman’s breast anatomy is different and mammography cannot identify all structures with complete precision. Thus, a woman with a benign breast lump may need other diagnostic procedures potentially including ultrasound, aspiration, and biopsy to exclude malignancy (Amin 2013; Miltenburg 2008; Jones 2011). Thyroid hormone irregularities, particularly hypothyroidism, should also be ruled out in women with fibrocystic breast conditions, as low thyroid function may be related to fibrocystic changes and the progression of breast cancer (Stoddard 2008; Patrick 2008; Smyth 2003).

Manual Breast Examination

A clinical manual breast exam (performed by a doctor) is often an early step in assessing breast symptoms. This exam involves palpating the breasts for lumps, and determining if discharge can be expressed. However, a manual breast examination will rarely be able to detect early-stage breast cancer and cannot be used in isolation to clearly differentiate among different benign breast disorders (Miltenburg 2008; Onstad 2013).

Women may perform breast self-exams to detect changes in their breasts. Fibrocystic breast tissue may feel thick, lumpy, or rope-like in texture, and the lump(s) are mobile and do not feel stuck to surrounding tissue. Lumps caused by fibrocystic breast conditions may become larger before each menstrual period and shrink after the menstrual period is over. Breast pain may occur in both breasts, and this pain may fluctuate throughout the menstrual cycle or remain constant. The most important consideration for women who examine their own breasts is to take note of changes in appearance or texture of breast tissue and to promptly report those changes to their health care provider, who can advise whether additional evaluation is necessary (NLM 2013; Scott-Conner 2015; NBCF 2012; Mayo Clinic 2013a).

Ultrasound

Ultrasound is often the only imaging study used to evaluate breast lumps in younger women. Ultrasound does not expose the patient to radiation. Instead, ultrasound uses sound waves to investigate the anatomy of the breast (Jones 2011; Miltenburg 2008; Gucalp 2014; NLM 2014).

Mammogram

A mammogram is an x-ray–based imaging procedure of the breasts. There are two types of mammogram: screening and diagnostic. Screening mammograms are performed on women with no signs or symptoms of abnormalities, and are meant to detect early-stage breast cancer. Diagnostic mammograms are used in women who have signs and symptoms of breast abnormalities in order to help differentiate cancer from benign conditions such as fibrocystic changes (NCI 2014). As a tool for detecting cancer, mammography is most useful in postmenopausal women. Younger women and those taking hormone replacement therapy often have dense breast tissue, which makes mammogram images less helpful. By themselves, mammograms do not identify all cases of cancer: follow-up of all imaging studies by means of cyst aspiration or biopsy is usually necessary for conclusive diagnosis (Miltenburg 2008; Evans 2002; Jones 2011; Onstad 2013).

One downside of mammograms is they expose women to a small amount of radiation (Jones 2011). Although not appropriate for all women, alternatives to mammography are available. Women interested in reading about breast cancer screening using mammography alternatives can refer to the Life Extension magazine article Breast Cancer Screening Alternatives.

Breast Biopsy

In women who receive a BI-RADS score of 4 or 5 after mammography or ultrasonography, a breast biopsy is often required (Eberl 2006; Kennedy 2011). There are several forms of breast biopsy available:

Fine needle aspiration. Fine needle aspiration is the least invasive type of breast tissue biopsy (Wesola 2013). In this procedure, the physician inserts a narrow gauge needle into the breast, removing a small sample of cells for analysis. Fine needle aspiration has a very low rate of complications and is associated with minimal discomfort. However, it requires a high degree of expertise on the part of the physician performing the procedure (Ljung 2001; Breastcancer.org 2015; Kaur 2007) and has become less favored than core needle biopsy in many breast cancer centers (Zervoudis 2014).

Core needle biopsy. A core needle biopsy is more invasive than fine needle aspiration and is associated with greater discomfort, though it has a low rate of complications. Some researchers prefer core needle biopsy, and it may be a more reliable method for distinguishing between in situ and invasive breast cancer compared to fine needle aspiration (Zervoudis 2014; Verkooijen 2002). Core needle biopsy is usually the first biopsy procedure used to evaluate breast lumps that cannot be easily palpated manually (Willems 2012; Al-Sobhi 1999; Verkooijen 2002).

Image-guided biopsy. If a mass that needs to be biopsied cannot be easily observed or localized, then the physician performing the biopsy may use imaging techniques to help guide the needle. A biopsy guided by mammography is called a stereotactic biopsy, and ultrasound imaging can be used to perform an ultrasound-guided biopsy (Huang 2014; BreastCancer.org 2015).

Surgical biopsy techniques. In cases where fine needle aspiration or core needle biopsy are inconclusive or provide results that are suspicious for cancer, incisional biopsy or excisional biopsy may be indicated (ACS 2014).

• In incisional biopsy, a physician uses manual instruments to cut through the skin and remove a piece of the suspicious tissue for examination. This procedure may be performed under sedation (BreastCancer.org 2015).
• Excisional biopsy is a surgical procedure performed under local anesthesia in which the entire area of suspicious tissue is removed. This procedure may be performed under sedation (ACS 2014; BreastCancer.org 2015).

Acetaminophen and NSAIDs

Acetaminophen or a nonsteroidal anti-inflammatory drug (NSAID) such as ibuprofen or naproxen are often considered first-line treatment for breast pain (Jones 2011; Sugg 2014; Kosir 2013). While these over-the-counter medications are usually effective at temporarily relieving mild-to-moderate breast pain, long-term, chronic use is associated with potentially severe side effects. For example, chronic NSAID use can cause gastrointestinal bleeding (Seager 2001; O'Neil 2012) and can damage the liver and kidney (Bessone 2010; Plantinga 2011).

Topical application of NSAID preparations directly to the breasts has proven effective for relief of both cyclical and non-cyclical breast pain. Importantly, unlike oral NSAIDs or acetaminophen, topical NSAIDs do not carry systemic risks to the gastrointestinal tract, liver, or kidneys (Qureshi 2005; Colak 2003; Kataria 2014). Professional medical societies have recommended topical NSAIDs for the treatment of breast pain (mastalgia), and some sources consider topical NSAIDs first-line treatment for mastalgia (Olawaiye 2005; Sugg 2014). Localized skin reactions are possible with topical NSAIDs (Klinge 2013).

Hormone-Related Treatments

For persistent, severe breast pain, medications that influence hormones may be recommended (Sugg 2014).

Oral contraceptives. Combined oral contraceptives (estrogen and progesterone) are sometimes recommended to help reduce symptoms of fibrocystic breasts, and are believed to work by supplying controlled amounts of estrogen and progesterone (Jones 2011). However, clinical trials of combined oral contraceptives for fibrocystic breast changes have yielded mixed results (Leonardi 1997; Carbonaro 2012).

Cabergoline. Cabergoline (Dostinex) is a drug that activates certain receptors for the neurotransmitter dopamine in the brain. One effect of this medication is the suppression of prolactin production in the pituitary gland (NIH 2012). Studies have shown that cabergoline helps reduce breast pain and other symptoms associated with fibrocystic breast changes (Aydin 2010; Castillo-Huerta 2013). It is not entirely clear why reducing prolactin levels helps treat fibrocystic changes, though sex hormone influence on the action of the pituitary gland may contribute (Srivastava 2007; Peters 1984). Another drug that functions similarly to cabergoline is called bromocriptine (Parlodel, Cycloset). Although there is some evidence that bromocriptine might help reduce symptoms caused by fibrocystic changes, cabergoline has been shown to perform better and cause fewer side effects in some studies (Aydin 2010; Castillo-Huerta 2013). Nevertheless, both of these drugs can cause serious side effects, such as intense nausea and neurological, psychological, and vascular problems (Mayo Clinic 2015b; Jones 2011; Onstad 2013).

Tamoxifen. When fibrocystic changes result in severe and chronic pain, physicians may prescribe a powerful drug called tamoxifen (Nolvadex, Soltamox) (Srivastava 2007; Jones 2011). Tamoxifen is best known as a treatment used in conjunction with chemotherapy for certain breast cancers. The usage of tamoxifen for breast pain is considered off label and should be supervised by a specialist (EBCTCG 2005; Jones 2011). Tamoxifen is effective for treatment of fibrocystic changes but has a significant side effect profile and is not often prescribed for this condition (Vaidyanathan 2002; Onstad 2013; Alvero 2015).

Danazol. Danazol (Danocrine) is currently the only drug approved by the Food and Drug Administration (FDA) for the treatment of breast pain, and in this capacity is used at a low dose, continuously for 3–6 months (Jones 2011). Danazol acts upon the pituitary gland in a way that suppresses estrogen and progesterone, and favors a masculine hormonal pattern (Beaumont 2002; NLM 2015). Sources differ regarding the effectiveness of danazol, but are in agreement that its serious side effect profile often makes it poorly tolerated (Alvero 2015; Onstad 2013; Goyal 2011). Among danazol’s side effects are masculinization symptoms (deepening of the voice, acne, abnormal hair growth patterns), vision problems, liver and lung problems, joint pain, irregular periods, and heart attack (NHS 2015).

Ormeloxifene (Centchroman)

Ormeloxifene, also known as centchroman, belongs to a class of drugs known as selective estrogen receptor modulators (SERMs). Ormeloxifene is a nonsteroidal compound that is manufactured and currently available in India as an oral contraceptive; some research on the drug is ongoing in the United States (de Barros 2015). A paper published in 2015 reported on a trial that compared ormeloxifene to tamoxifen for the treatment of breast pain. The effectiveness of the two medications after 12 weeks was similar, though side effects such as dizziness, menstrual irregularities and development of ovarian cysts were greater in the ormeloxifene group (Jain 2015). A three-month randomized controlled trial in 121 women aged 20–50 compared 30 mg ormeloxifene twice per week to placebo for the treatment of breast pain and lumps. Compared with placebo, both breast pain and breast lumps were significantly reduced by ormeloxifene treatment (Kumar 2013).

In another trial ormeloxifene significantly reduced breast pain to a greater degree than danazol; nearly 90% of women had relief in the ormeloxifene group, while 69% taking danazol experienced pain relief (Tejwani 2011). In another study, 86% of women taking ormeloxifene for 24 weeks had complete resolution of breast pain (Sharma 2012).

As some researchers have expressed concern with ormeloxifene’s side-effect profile (Jain 2015), women interested in this drug should consult closely with their health care provider to weigh the risks and benefits.

Near-Infrared Imaging with Contrast

The primary concern in the assessment of breast symptoms is to correctly differentiate between benign breast changes and serious breast diseases such as breast cancer. An experimental procedure, near-infrared imaging with the use of contrast, has shown an ability to increase diagnostic accuracy when combined with mammography and ultrasound. Multiple studies have shown that cancerous breast tissue tends to absorb more contrast media than benign tissue. This difference can be detected using a scanner that detects near-infrared energy. Preliminary evidence is promising, but this innovative diagnostic approach is still in development. Like other imaging methods, this approach is minimally invasive, though the contrast material must be injected into a vein (Hawrysz 2000; Poellinger 2012). More research is needed to determine the true utility of near-infrared imaging in detecting fibrocystic changes and differentiating them from breast cancer.

Dietary factors appear to play an important role in the development of both benign fibrocystic changes and breast cancer, and specific components of a healthy diet may significantly reduce the risk of developing fibrocystic changes and benign breast disease (Frazier 2013; Baer 2003; Berkey 2013; Su 2010). For instance, dietary fiber improves estrogen metabolism, and diets high in fiber have been associated with reduced incidence of some benign breast disorders (Jones 2011).

A study in 675 women with benign breast conditions, compared to 1070 healthy controls, found that greater consumption of fruits and vegetables decreased the risk of proliferative fibrocystic breast conditions and breast cancer. This effect was most clear when comparing the one-quarter of women with proliferative breast conditions or breast cancer who ate the most fruits and vegetables to controls (Li 2005). A similar finding on the importance of diet came from a study that compared 121 women with benign breast disease to 121 women with non-breast related conditions. This study found that several dietary components were associated with significantly reduced odds of benign breast disease. Higher citrus fruit consumption was associated with 57% reduced odds, and higher non-citrus fruit with 65% reduced odds (Galvan-Portillo 2002).

Several studies have shown that women who consume more vegetable fats, vegetable protein, fiber, and nuts, and less animal fat, red meat, and alcohol are less likely to develop fibrocystic and benign breast changes later in life. Studies have yet to determine if adult women who adopt this dietary approach are at reduced risk of fibrocystic changes, but this strategy, as reflected in a Mediterranean dietary pattern, has been shown to reduce breast cancer risk in adult women. Thus, a fiber-rich, plant-based diet high in healthy fats from sources such as olive oil and fish, and low in red meat, is a reasonable preventive strategy (Frazier 2013; Baer 2003; Berkey 2012; Berkey 2013; Su 2010; Kakkoura 2015; Castello 2014; de Lorgeril 2014; Escrich 2011).

Chasteberry (Vitex agnus-castus)

Chasteberry, also known as Vitex agnus-castus, is commonly used for breast pain in Europe (van Die 2013), and the German Commission E (a regulatory body that oversees dietary supplements in Germany) supports the use of Vitex agnus-castus for the treatment of breast tenderness, especially premenstrually (Altern Med Rev 2009).

In a randomized controlled trial in 97 women with cyclical breast pain, daily dosing with a solution containing about 32.4 mg of chasteberry extract significantly reduced breast pain compared with placebo. The improvement was observed over two menstrual cycles, and half of the patients receiving chasteberry extract reported that they were free from severe pain after the second treatment cycle, with some women reporting that pain relief was noticeable beginning with the first cycle (Halaska 1999). Chasteberry is believed to exert its effect through inhibition of excessive release of the hormone prolactin by means of activity at dopamine receptors in the pituitary gland (Carmichael 2008; Wuttke 2003). This mechanism of action is similar to that of the drug bromocriptine. According to a rigorous review of the literature, chasteberry benefits other conditions influenced by hormonal fluctuations, including premenstrual syndrome, and menstrual cycle irregularities (van Die 2013; Altern Med Rev 2009).

A randomized trial compared chasteberry extract and bromocriptine in the treatment of 40 women with cyclical breast pain and 40 women with mildly elevated prolactin secretion. Prolactin secretion and breast pain were significantly reduced by both treatments. The authors pointed out that the necessity of long-term treatment of breast pain makes tolerability and low toxicity a priority, so patients are more likely to adhere to treatment with chasteberry extract (Kilicdag 2004).

Lignans, Flaxseed, and Enterolactones

Lignans are polyphenolic compounds present in a variety of plant foods, with high concentrations found in flaxseeds and sesame seeds, as well as in certain plant extracts such as Norway spruce (Pandey 2009; Willför 2003; Liu 2006). Plant lignans are converted by intestinal bacteria to the biologically active “mammalian lignans” such as enterolactone (Lampe 2003; Liu 2006; Higdon 2010). Enterolactones have been shown to concentrate in breast cyst tissue and potentially mitigate breast cancer risk in certain patients (Boccardo 2003). Both lignans and enterolactones have been studied in pre-clinical settings and observational studies, and found to have substantial anticancer activity. This quality is particularly evident in protection from breast cancer abnormalities, and in an association with reduced breast cancer risk (Fabian 2010; Thompson 1996; Guglielmini 2012; Suzuki 2008; Boccardo 2004).

Enterolactones appear to have aromatase-inhibiting activity (Adlercreutz 1993; Lu 2012). Aromatase is the enzyme responsible for creating estrogen from precursor compounds (Bulun 2005). This property could account for the ability of enterolactones to protect against breast cancer and benign breast changes (Su 2010). Tamoxifen is one of the few drugs used to treat fibrocystic changes and severe breast pain, but is associated with significant side effects. Since fibrocystic changes are known to be closely associated with female sex steroids, and possibly with estrogen excess, dietary and supplemental lignans may be one of the more promising approaches to managing benign breast changes (Sugg 2014; Jones 2011; Vaziri 2014).

A population-based study compared the diets of 121 women with benign breast disease and 121 control women. Women who consumed the most food sources of lignans were 52% less likely to have benign breast changes than those with the lowest consumption of these foods (Galvan-Portillo 2002).

In a randomized controlled trial, 56 women with severe cyclical breast pain were given a 25 g flaxseed-containing muffin daily, while 60 women received a placebo muffin. The treatment phase of the trial lasted three months, during which the women assessed breast pain, swelling and lumpiness each cycle, as well as daily breast pain. Median reduction of pain score was significantly greater in the flaxseed group compared to placebo at the end of three cycles. There were no significant side effects. Lignans measured in urine increased in the flaxseed group (Goss 2000).

A randomized trial in 181 women with cyclical breast pain assigned participants to receive either 30 g flaxseed per day in specially prepared bread; plain bread without flaxseed; or a capsule containing a modest amount of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The intervention lasted for two menstrual cycles. The severity of breast pain was significantly reduced by about 56% in the flaxseed group, 17% in the plain bread group, and about 42% in the omega-3 group (Vaziri 2014).

Two professional organizations endorse flaxseed consumption for the treatment of benign breast conditions. The Society of Obstetricians and Gynecologists of Canada recommends flaxseed as first-line treatment for cyclical breast pain (Rosolowich 2006), and the Canadian Cancer Society recommends consumption of flaxseed for fibrocystic breast changes (CCS 2015).

Vitamin E

Vitamin E was shown to be effective in reducing the most severe premenstrual breast pain, and showed a trend towards overall reduction of cyclical breast pain, in a trial that compared vitamin E, evening primrose oil, a combination of the two, and placebo (Pruthi 2010). Another study compared women with existing proliferative abnormalities to women with non-proliferative conditions or women who did not require a breast biopsy. This study found that women with the highest serum concentration of alpha- and gamma-tocopherol, two forms of vitamin E, showed a trend towards lower risk of both proliferative disease without atypia and breast cancer. Women with the highest consumption of vitamin E from food had a significantly lower risk of breast cancer, and a similar trend was present for those with the highest consumption of vitamin E from both supplements and food (London 1992). A dietary study among girls found that those who consumed the most vitamin E during adolescence had a significant 21% lower risk of proliferative benign changes as adults compared with those who consumed the least vitamin E (Baer 2003).

Evening Primrose Oil and Gamma-Linolenic Acid

Evening primrose oil may relieve breast pain (Vaidyanathan 2002; Kosir 2013). Gamma-linolenic acid (GLA), which is believed to be the active constituent of evening primrose oil, may also be useful in this context (Sugg 2014). It is important to note that up to four months of treatment with evening primrose oil may be necessary for breast pain relief (Onstad 2013).

A randomized controlled trial compared six months of 3 g evening primrose oil, 1200 IU vitamin E, a combination of the two, or placebo each day in 41 women with premenstrual breast pain. All three treatments reduced the most severe pain, with the clearest effect for evening primrose oil alone; there was a trend for all three treatments to reduce the incidence of cyclical breast pain (Pruthi 2010).

Iodine

Iodine may be necessary for normal function of breast tissue, and iodine deficiency has been shown, in preclinical and clinical trials, to be related to precancerous and cancerous changes in breast tissue (Eskin 1977; Patrick 2008). In rodents, dietary restriction of iodine creates a syndrome very similar to fibrocystic changes (Krouse 1979), and in another study, supplementing rodents with iodine was shown to suppress breast tumor growth (Funahashi 1996). Lower incidence of benign breast disease occurs in Japanese women, and some researchers hypothesize that this may be related to greater iodine intake in this population, via consumption of seaweed (Cann 2000).

A review of three clinical studies found that treating women who had fibrocystic breast changes with iodide or iodine led to clinical improvement in about 70% of cases. Side effects of iodine treatment, which included changes in thyroid hormone levels, acne, headaches, thinning hair, and others, occurred in about 11% of subjects in one of the studies (Ghent 1993).

Omega-3 Fatty Acids

Supplementation with the beneficial omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may effectively reduce cyclical breast pain and lower the risk of fibrocystic breast changes.

A randomized trial gave one group of women with cyclical breast pain a daily omega-3 supplement containing 180 mg EPA and 120 mg DHA. In this group, pain intensity was significantly reduced by about 42% after two cycles among women who received the omega-3 supplement, while women who did not receive the omega-3 supplement experienced a reduction of only about 17% (Vaziri 2014).

In another study, women with the highest EPA concentration in their red blood cells had a 62% lower risk of developing fibroadenoma compared with women with the lowest EPA concentrations (Dijkstra 2010). Similar research found that women with the highest red blood cell EPA concentration had a 67% lower risk of non-proliferative fibrocystic changes than women with the lowest red blood cell omega-3 concentrations (Shannon 2009).

Vitamin D

Vitamin D deficiency is strongly linked to breast cancer risk and may be associated with fibrocystic changes. A study that compared vitamin D levels in women with no breast lumps, fibrocystic changes, or breast cancer found that severe vitamin D deficiency (blood levels of less than 12.5 ng/mL) increased the risk for breast cancer by threefold. Importantly, women with fibrocystic changes had vitamin D levels higher than women with breast cancer but lower than healthy controls (Alipour 2014). One trial found that women who consumed more than 533 IU vitamin D per day from diet and supplements showed a trend towards lower incidence of proliferative benign breast changes (Rohan 2008). A survey in 682 women with proliferative breast changes found that those in the highest one-fifth of vitamin D intake during adolescence had a 21% lower risk of proliferative benign changes compared with women whose intake was in the lowest one-fifth as adolescents (Su 2012).

Indole-3-Carbinol and Diindolylmethane

Indole-3-carbinol (I3C) and diindolylmethane (DIM) are related molecules found in cabbage family vegetables such as broccoli, kale, and cauliflower. I3C is metabolized in the body to form DIM, a biologically active compound. I3C and DIM can modulate estrogen receptor activation and estrogen metabolism, properties that may help counter the known role of estrogen excess in fibrocystic changes (Weng 2008; Higdon 2008). Neither I3C nor DIM have been studied in clinical settings in the treatment or prevention of fibrocystic changes; however, rats treated with dietary I3C showed a reduction in the incidence of fibroadenomas (Kojima 1994). More studies are needed before conclusions can be reached about the role of I3C and DIM in the treatment of fibrocystic changes (Weng 2008).

Resveratrol

A study in which higher consumption of fruits and vegetables significantly decreased the risk of proliferative fibrocystic breast conditions and breast cancer also found that higher consumption of grapes was especially associated with a lower risk of proliferative fibrocystic breast conditions and breast cancer. The authors of this study pointed out that resveratrol, a natural polyphenolic compound present in grapes and related foods, has powerful anticancer effects (Li 2005; Vang 2011).