Mastalgia

Etiology

The exact etiology of mastalgia remains undefined; however, potential causes of breast pain can be classified into 3 major categories: cyclic, noncyclical, and extramammary. The categorization of the underlying etiology of mastalgia often guides management.[6][7][8]

Cyclic Mastalgia

Cyclic breast pain, the most common type of mastalgia, is primarily caused by physiologic hormonal changes associated with the menstrual cycle or exogenous hormones cyclically administered (eg, contraception, ovulation induction, regulation of menstrual cycles).[9] Periodic discomfort in the breasts could be considered physiologically normal, as increased estrogen levels stimulate ductal elements. Additionally, decreased progesterone stimulates breast stroma, and increased prolactin stimulates ductal secretion. These hormonal changes are regular events during the menstrual cycle in women of reproductive age, which can result in cyclical breast pain.[10]

Cyclic mastalgia can also be associated with varying hormonal levels due to nonmenstrual-related physiologic states, including pregnancy, lactation, perimenopause, and postmenopausal hormonal therapy. Unpredictable, intermittent increases in estrogen during perimenopause or increased breast tissue volume and vascularity during pregnancy and lactation may cause breast pain and fullness. Factors, eg, caffeine, smoking, and dietary fat intake, may also exacerbate symptoms, though their influence remains inconclusive.[11][12][13] Conversely, some cases have shown amelioration of pain during pregnancy, with lactation, and with the onset of menopause. Furthermore, physiologic etiologies of mastalgia have been reported in transgender individuals as a result of treatments, eg, breast procedures, hormonal injections, binding, and mastectomy.[5] Between 20% and 30% of cyclical breast pain resolves spontaneously. However, as much as 60% of cases will have recurring episodes.[14]

Noncyclic Mastalgia

Noncyclic breast pain, accounting for one-third of cases, is more associated with structural or anatomic etiologies rather than hormonal influences. Diagnostic studies are more likely to identify the cause of noncyclic mastalgia than cyclic breast pain. Noncyclic mastalgia usually affects women aged 40 years or older, often perimenopausal. Noncyclical breast pain is found to be caused by malignancy in up to 4.6% of cases; therefore, clinicians should exclude any neoplastic, inflammatory, or vascular disease.[15][5] Pain can be intermittent or constant, with spontaneous resolution in 50% of patients. Noncyclical pain is variable and most commonly unilateral.[14][3] Structural causes of noncyclic mastalgia related to breast or chest wall lesions include: 

• Breast cystic or solid masses
• Stretching of Cooper ligaments by large, pendulous breasts
• Ductal ectasia causing inflammation, fever, and pain secondary to duct dilatation produced by the entrance of lipid material through the duct wall [16]
• Mastitis or breast abscess
• Breast malignancy
• Breast surgery or trauma
• Thrombophlebitis of subcutaneous breast and chest wall veins as in Mondor disease [15][17][5][11]

Extramammary Mastalgia

Extramammary mastalgia is also noncyclical but primarily refers to breast pain that originates from a location outside the breast, eg, the heart, lung, chest wall, or esophagus. Extramammary breast pain is felt primarily within the breast tissue but, in fact, is a referred pain from another origin or caused by an etiology outside of the breast. For example, referred pain originating from the chest wall (costochondritis), gastroesophageal reflux disease, cardiovascular disease, herpes zoster infection, or gallbladder and stomach disease may give a false impression of breast pain.[11][18]

Additionally, injuries from musculoskeletal sources can lead to chest wall pain related to muscle injury (related to pectoralis major muscle) from repetitive activities, scarring from prior biopsy, intercostal neuralgia, and Tietze syndrome, among other spinal and paraspinal disorders.[15][3][19][20] The use of certain medications has also been implicated with breast pain, which includes oral contraceptive pills, estrogen and progesterone hormonal therapies, certain antidepressants like selective serotonin reuptake inhibitors, and antihistamines.[5] Mastalgia has been associated with psychosomatic disorder in a study that demonstrated an increased incidence of breast pain in patients with depression and anxiety.[18]

Epidemiology

In general, mastalgia is more common in women 30 to 50 years of age.[14] Experts estimate that 70% of women in the United States experience breast pain during their lifetime, of which around 30% seek medical attention. Of those patients who present to a clinician for evaluation of mastalgia, 20% have severe symptoms.[21][12] The peak age of incidence for cyclic mastalgia is 20 to 30 years of life. The incidence decreases with increasing age and early pregnancy and is less commonly found in postmenopausal women. Noncyclic mastalgia has a higher prevalence in women aged between 30 and 40.[22] Many female patients with breast pain report a negative impact on their life quality. Up to 40% of women will describe interference with sexual activity, interference with physical activity by 30%, and impact on work and social activities in 10% of patients.[23] Mastalgia is uncommon in men but has been documented in male patients with conditions, eg, gynecomastia and hormonal dysfunction.[5] 

The worldwide prevalence of breast pain varies depending on the population being studied. A study was conducted on women from the United Kingdom using a survey to correlate physical activity with the prevalence, severity, and frequency of breast pain. This study showed a relationship between an increased prevalence of breast pain and a low level of physical activity. However, the severity of pain did not vary between either group.[24] The prevalence of breast pain can vary depending on the region as well as ethnicity. Women in the United Kingdom report a 60% incidence of breast pain, while women of Asian ethnicity have been found to have a breast pain prevalence of 5%.[25]

Pathophysiology

The exact pathophysiologic mechanisms that underlie mastalgia are unclear but are thought to be influenced by hormonal, structural, and systemic factors. Cyclic mastalgia often occurs during the luteal phase of the menstrual cycle, driven by rising progesterone levels. These hormonal shifts lead to breast tissue changes, including lobule enlargement, basal epithelial cell proliferation, and stromal edema, which manifest as breast fullness and pain. Imaging studies during this phase reveal increased T2 signal on magnetic resonance imaging, reflecting stromal edema. Altered estradiol and prolactin levels may also contribute, while decreased luteal progesterone has been implicated in exacerbating symptoms.[5][26]

In noncyclic mastalgia, changes are more varied and include localized inflammation, as seen in idiopathic granulomatous mastitis or mastitis, and structural changes, eg, breast cysts, fibroadenomas, or macromastia. Hormonal variations during pregnancy and menopause further influence breast tissue, with increased estrogen and progesterone levels in pregnancy driving ductal and lobulo-alveolar proliferation and vascular changes, often accompanied by pain and fullness. Postsurgical and medication-related changes (eg, lymphedema or estrogenic effects from contraceptives) can alter breast physiology and contribute to pain. These diverse pathophysiologic mechanisms underline the complexity of mastalgia and highlight the need for targeted evaluation and management strategies.[5][26] Drinking caffeinated beverages may be associated with overstimulation of breast cells due to impaired adenosine triphosphate degradation by methyl xanthine.[26] Some other causes, including the consumption of a high-fat content diet, smoking, and use of certain medications (eg, antidepressants, antibiotics, and antihistamines), have also been linked with mastalgia, but their exact pathophysiology is unknown.[23]

History and Physical

Clinical History

A detailed history and physical exam are the first and foremost steps in delineating the course of investigation and treatment plan. A history of the nature of pain, its location, severity, onset, and associated symptoms should be obtained. A pain diary may help identify a cyclic or noncyclic pain pattern and provide valuable information leading to an accurate diagnosis.[27] Additionally, clinicians should inquire about medication history and family history of breast cancer.[22]

Cyclic breast pain, the most common type, is experienced by about two-thirds of affected women. Cyclic mastalgia is typically described as recurrent, bilateral, diffuse breast tenderness, intensifying during the luteal phase and subsiding with menstruation, though cases with unilateral pain have been reported as well.[5] Breast pain associated with the menstrual cycle due to hormonal variation is often also associated with breast swelling and lumpiness.[5] 

Noncyclic breast pain, accounting for one-third of cases, is characterized as a unilateral, continuous or erratically occurring, localized pain unrelated to the menstrual cycle. Noncyclic mastalgia may be associated with large breasts, cystic or solid masses, pregnancy, trauma, prior breast surgery, or inflammatory conditions like mastitis and abscesses.[5] Extramammary mastalgia is characterized by noncyclical breast pain that is unilateral and frequently occurs in the outermost medial or lateral aspects of the breast. Clinical history of the onset of pain with activity is often associated with extramammary mastalgia.[11]

Physical Examination Findings

The physical examination further helps to identify any features that need further evaluation (eg, palpable breast mass).[22] Emphasis should be made to explore the chest wall along with breast examination to differentiate extramammary pain from true mastalgia. Characteristics of breast pain that strongly suggest an extramammary etiology include unilateral location, very lateral or medial location in the breast, and precipitation of chest pain by applying pressure on a specific area of the chest. The breast should be adequately explored with the review of all 4 quadrants. Supraclavicular, infraclavicular, and axillary regional lymph nodes should be palpated, and the breast should be examined for any lump, skin changes, nipple retraction, color change, ulceration, swelling, or edema, inflammation, scars, or abnormal nipple discharge.[1] The examination should also involve elevating breast tissue with 1 hand and palpating the underlying chest wall with the other to look for any chest wall deformity.[19][28] Any abnormal finding identified is carefully documented, and the patient should be referred for further evaluation.[22]

Evaluation

Diagnostic Imaging Indications for Mastalgia

In patients with cyclic or diffuse noncyclic mastalgia and no abnormal findings on clinical breast examination (eg, breast mass, skin changes, nipple discharge) or high-risk factors, no further diagnostic studies are necessary; reassurance is typically sufficient. However, diagnostic imaging is indicated in women with noncyclical focal mastalgia or an abnormal finding on clinical examination. Abnormalities on clinical breast examination should be evaluated as the primary clinical pathology, even if mastalgia was the presenting symptom.[29] Any extramammary mastalgia should be evaluated as indicated by the underlying etiology.[5]

Diagnostic Imaging Recommendations

The most common radiological modalities for imaging breast tissue are mammography, ultrasound, and magnetic resonance imaging (MRI). However, for the evaluation of mastalgia alone, MRI is not indicated. Age-specific recommendations have been established to optimize the effectiveness of these diagnostic studies. In lactating patients, initial imaging recommendations follow age-specific guidelines. However, ultrasound is preferred for initial imaging in pregnant individuals.[28] Breast imaging findings are classified by their Breast Imaging Reporting and Data System (BI-RADS) category, which correlates imaging findings with their probability of underlying malignancy and recommends a broad treatment strategy.[30] Please see StatPearls' companion resource, "Breast Imaging Reporting and Data System," for further information on this imaging classification system. The following imaging guidelines have been proposed by the American College of Radiology Appropriateness Criteria for the evaluation of new palpable breast masses based on the patient's age:

• For women 40 years and older: Either diagnostic mammography or digital breast tomosynthesis (DBT) is recommended as the initial imaging modality.[31] If initial imaging has BI-RADS 1 to 3 findings, ultrasound is recommended to characterize any lesions further. Ultrasound is also recommended if mammogram imaging is unable to visualize a palpable mass, as 40% of benign palpable masses are only seen on ultrasound.[9][31][32]
• Women younger than 30: Ultrasound imaging is the preferred initial modality in these women.[22] Ultrasound is preferred for women younger than 30 due to denser breast tissue and lower cancer incidence in this group.[9][31] If ultrasound results show BI-RADS 1, a diagnostic mammogram is appropriate for high clinical suspicion.[31][32]
• Women aged between 30 and 39: Ultrasound, DBT, and mammography may be considered for initial imaging. However, diagnostic mammography is preferred in high-risk patients or those with suspicious findings on breast exam, as mammogram facilitates clinical assessment of the disease extent in women older than 30. Concordance between imaging findings and clinical examination is essential for accurate diagnosis.[9][31][32]

Please see StatPearls' companion resource, "New Breast Mass," for further information on recommended diagnostic evaluation of breast pathology.

Breast Biopsy

In the infrequent case of a patient with mastalgia and imaging findings suspicious of malignancy, a tissue biopsy is required. Pathology analysis involves either fine-needle aspiration biopsy (FNAB) or core biopsy.[16] Cytology allows the analysis of cells in isolation, while histological examination of a biopsy can provide more detail about the architecture of tissues. These invasive procedures involve risks to the patient and should, therefore, only occur when the index of suspicion is present.

Whether to perform FNAB or core biopsy depends on several factors, including the expertise of the clinician, available diagnostic equipment, and the site of the lesion. However, core biopsy is generally preferred over FNAB due to its decreased incidence of insufficient tissue collection and higher sensitivity and specificity than FNAB.[33][9] Breast cancers diagnosed with an FNAB require core needle biopsy confirmation with immunohistochemical evaluation before treatment is initiated.[34] Please see StatPearls' companion resources, "Fine Needle Aspiration of Breast Masses" and "Stereotactic and Needle Breast Biopsy," for more information on these procedures.

Treatment / Management

Depending on the results of clinical assessment and any diagnostic studies performed, patients without any identifiable pathology typically can be managed with reassurance and supportive therapies, if desired. Up to 85% of women with mastalgia will show alleviation of pain episodes after receiving reassurance that the evaluation has no findings of breast cancer. Reassurance alone results in spontaneous resolution of mastalgia within 3 months in 20% to 30% of women, most likely due to a decrease in anxiety.[5] The remaining 15% will require treatment apart from reassurance, mainly because of the negative impacts on physical activity (30%) and sexual activity (up to 40%), as well as their life quality in work and social activities (10%).[21][23][3]

General Supportive Measures

Following the exclusion of an underlying breast malignancy or significant etiology, patients with persistent mild to moderate mastalgia may be treated with conservative interventions. Although clinical studies do not show a definitive benefit, this first-line pain-relieving supportive therapy should be given a trial before moving to second-line pharmacologic treatment. Recommended supportive therapies include:

• Well-fitting bra: Increasing the breast's physical support with supportive garments, eg, a well-fitted brassiere. Literature shows that approximately 70% of women wear an incorrect size of supportive breast garment.[35] Women with large breasts or who are physically active benefit from a soft, supportive garment that reduces the stretching of the Cooper ligament, with studies demonstrating improved pain in up to 85% of these patients.[5][36]

• Relaxation therapy: An older study found the use of relaxation therapy can help patients relieve high levels of anxiety and depression associated with mastalgia.[1] A recent study suggested that yoga and meditation may have some benefits in patients with cyclic mastalgia.[37]
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• Exercise: Increased physical activity while wearing a supportive sports bra may improve mastalgia, especially in overweight women.[5] The inclusion of an exercise routine may improve mastalgia as a result of the release of endorphins.[35]

• Dietary modifications: Avoidance of foods and beverages associated with increased breast pain, including methylxanthines found in coffee, chocolate, tea, and some soft drinks, and saturated fatty acids, may help to mitigate symptoms.[38] Instead, patients should increase consumption of unsaturated fatty acids and fiber.[10][22]

• Nutritional supplements: Nutritional supplementation of vitamins E and D, evening primrose oil (EPO), and soy have been suggested as beneficial therapies in some women.[5][22] EPO contains the fatty acid gamma-linolenic acid, a precursor of prostaglandin E1. Vitamin E, as an antioxidant, also plays a vital role in alleviating breast pain. Using 200 IU of vitamin E twice daily with evening primrose oil for 3 months showed progressive improvement in symptoms of premenopausal women with cyclic breast pain in some studies. However, they should be discontinued if no improvement is observed after 4 to 6 months.[10][39] Though the mechanism is unclear, such therapies generally have no adverse effects, and some physicians endorse their use if they relieve patients.[10][40]
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Pharmacological Therapy

Medications, other than analgesics, are used as second and third-line management options, though referral with a subspecialist is recommended due to various adverse effects associated with these treatments.[5] For patients with severe pain or mastalgia unresponsive to supportive therapy, the following pharmacologic treatments may be considered:

• Analgesics: NSAIDs, acetaminophen, ibuprofen, and topical (diclofenac in patch or gel form) are effective in up to 80% of women with mastalgia while having minimal adverse effects.[41] These agents are recommended as first-line pharmacological treatments; however, topical (eg, ibuprofen or diclofenac in patch or gel) forms are preferred to avoid adverse gastrointestinal effects.[41][5][22]
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• Tamoxifen: Out of the prescription medication treatments, tamoxifen, a selective estrogen receptor modulator, is the most effective for mastalgia management, with up to 96% of women with cyclic breast pain and 56% of women with noncyclic breast pain demonstrating improvement in studies. Adverse effects include deep venous thrombosis, endometrial cancer, hot flashes, nausea, cataracts, joint pain, leg cramps, and weight gain; therefore, tamoxifen should not be used for >6 months.[5] Recommended effective doses for use are 10 to 20 mg daily.[8][19][42][43] Patients should be questioned regarding an increased risk for some of these conditions before initiating this medication.
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• Danazol: Although recommended as a second-line prescription agent to tamoxifen, this is the only US Food and Drug Administration (FDA) approved medication to treat mastalgia.[5] However, danazol is contraindicated in pregnancy, lactation, and thromboembolic disease. The recommended dose is 200 mg daily, taken during the luteal phase of the menstrual cycle, with a reduction to 100 mg daily after symptomatic improvement.[5] This dosing regimen helps to optimize the effectiveness of the medication and reduces adverse effects, eg, menstrual irregularity, weight gain, hot flashes, and deepening of the voice, which often cause patients to discontinue treatment.[41][44] Danazol is also preferred over bromocriptine (2.5 mg twice daily), which, though effective in reducing breast pain, is less effective than danazol and has more severe adverse effects. FDA approval was removed from bromocriptine due to adverse effects, including hypotension, dizziness, and death.[22]
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• Goserelin: Gonadorelin analogs, which are used for ovarian suppression, may be considered in extreme cases but are reserved for refractory mastalgia and are limited to 6 months of treatment. Adverse effects include hot flashes, decreased libido, and irritability.[5][22]

In general, noncyclic mastodynia responds more poorly to treatment than cyclic mastodynia. However, 50% of noncyclic cases will resolve spontaneously. While cyclic mastalgia more reliably responds to treatment, up to 60% of cases could recur after ceasing therapy.[2]

Differential Diagnosis

Mastalgia is a symptom shared by a wide array of conditions, though the primary differential of concern for patients is breast cancer. However, an extremely low percentage of patients with breast pain will be diagnosed with this condition. Differential diagnoses that should be considered when evaluating mastalgia include:

• Cyclical mastalgia
  • Hormonal fluctuations during the menstrual cycle
  • Premenstrual tension syndrome 
  • Fibrocystic breast changes
• Noncyclical mastalgia
  • Idiopathic granulomatous mastitis
  • Macromastia-related pain
  • Breast cysts or fibroadenomas
  • Post-surgical breast pain syndrome
  • Medication adverse effects (eg, contraceptives, SSRIs, digoxin)
  • Referred pain from musculoskeletal conditions (eg, costochondritis)
  • Structural causes (eg, ill-fitting bras, macromastia)
• Infectious or inflammatory conditions
  • Mastitis (lactational or nonlactational)
  • Breast abscess
  • Inflammatory breast cancer
  • Herpes simplex or dermatitis
• Pregnancy and lactation-related conditions
  • Engorgement
  • Milk stasis
  • Nipple vasospasm or trauma
  • Candidiasis or nipple eczema
• Neoplastic conditions
  • Breast cancer (rarely presents with pain)
  • Phyllodes tumor
  • Infarction within a fibroadenoma
• Systemic conditions
  • Fibromyalgia
  • Cardiovascular (eg, referred pain from ischemic heart disease)
  • Gastrointestinal (eg, referred pain from peptic ulcer disease)
  • Respiratory (eg, referred pain from pleuritis or pneumonitis)
• Psychological conditions
  • Anxiety
  • Stress-related pain [7][5]

Prognosis

The prognosis of mastalgia depends on the underlying pathological or psychological cause. However, cases of breast pain with no identified underlying pathology will show high rates of spontaneous remission in a period of 3 months to up to 3 years.[45] The prognosis is affected by the age at which the pain episodes first started and the category of its etiology.

Noncyclical pain, although it shows a poor response to therapy, will result in spontaneous resolution in up to 50% of women. Some of this resolution may be attributable to a hormonally mediated event such as pregnancy or menopause.[14] For women with cyclical breast pain, around 60% of patients will show a relapsing and remitting course of pain episodes, with some presenting with recurrent symptoms 2 years after therapy. However, 20% to 30% of women with cyclical pain will show spontaneous resolution within 3 months.[14][15]

Complications

In the majority of cases, the complications seen in patients with mastalgia are treatment-related. Adverse effects, including nausea, bloating, headache, vaginal dryness, hot flashes, leg cramps, weight gain, and menstrual irregularities, are most commonly associated with pharmacological treatment modalities, eg, danazol and tamoxifen. Therefore, clinicians should ascertain if the patient has a history of such symptoms or contraindications to treatment before starting these therapies.[46]