Mastalgia

Etiology

The exact etiology of mastalgia remains undefined.[2] However,  increased sensitivity of breast tissue towards the hormonal variation during the menstrual cycle plays a vital role in the development of cyclic mastalgia. Moreover, this cyclic pain often abates with pregnancy or menopause, which further strengthens the etiologic role of hormonal fluctuations.

Non-cyclic breast pain results from changes in the anatomical structure like the development of breast cyst, prior breast trauma or surgery, injury to the chest wall, muscle, or joint, intercostal neuralgia, Tietze syndrome, and other spinal and paraspinal disorders which can cause referred breast pain.[5]

The use of certain medications has also been implicated with breast pain, which includes OCPs (oral contraceptive pills), estrogen and progesterone hormonal therapies, certain antidepressants like SSRI (selective serotonin reuptake inhibitors), and antihistamines.

Some studies claim that anxiety, stress, and depression are contributing factors. In contrast, a few others mention that caffeinated drinks, fatty diet, and smoking also play a major role in its development.[6]

Epidemiology

Mastalgia is considered to be the most common breast complaint with which a female presents in her reproductive age. About 70 percent of women in the US suffer from this condition during their lifetime, out of whom only 30 percent seek medical help. The peak age of incidence for cyclic mastalgia is 20 to 40 years of life. The incidence decreases with increasing age and early pregnancy and is less commonly found in postmenopausal women.

Many females having breast pain reported a negative impact on their lives, especially interference with sexual activity (40% females), physical activity (30% females), and negative impact on work and social activities (10% females).[7] The prevalence of breast pain also varies depending on ethnicity. Women of Asian ethnicity report breast pain in 5% of the population, while studies conducted in the UK showed a 60% incidence in British women.

Pathophysiology

Cyclic breast pain, which is related to hormonal changes, is predominantly associated with the luteal phase of the menstrual cycle and improves with the onset of menses. The periodic discomfort is caused by the increase in estrogen levels that stimulate the breast's ductal elements while simultaneously decreasing progesterone stimulation of stroma. A concurrent increase in prolactin, causing increased ductal secretion, also contributes to pain and swelling during this phase. Association of cyclic mastalgia with the use of hormonal therapy such as oral contraceptives and hormone replacement therapy, with its resolution during pregnancy/lactation and menopause, also justifies its hormonal etiology.[8]

Non-cyclic breast pain is not hormone-related and may be inflammatory, vascular, muscular, or neoplastic in origin. It has an unusual pattern with intermittent or constant pain, a variable location, and is most likely unilateral. A few of the common causes include breast cysts, fat necrosis due to trauma, mastitis or breast abscess, duct ectasia [because of duct dilation with periductal inflammation], and costochondritis or chest pain due to angina.[5]

Some other causes like the consumption of high-fat content diet, smoking, drinking caffeinated beverages, and use of certain medications (antidepressants, antibiotics, antihistamine) have also been linked with mastalgia, but their exact pathophysiology is unknown.[9]

History and Physical

A detailed history and physical exam are the first and foremost steps in delineating the course of investigation and treatment plan. History regarding the nature of pain, its location, severity, and onset, and the use of a pain diary to chart out its cyclic or noncyclic pattern can provide valuable information leading to an accurate diagnosis. 

The physical examination further helps to identify any alarming feature that needs special attention. Emphasis should be made to explore the chest wall along with breast examination to differentiate extramammary pain from true mastalgia. 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. 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.[10][11] Any abnormal finding identified is carefully documented, and the patient should be referred to a specialist for further evaluation.

Evaluation

Imaging modalities most commonly used to evaluate any abnormal physical exam findings include mammography and breast ultrasound. The primary aim of such testing is to rule out any serious pathology (breast cancer) underlying a suspicious finding. Young females with cyclic mastalgia, which is bilateral and non-focal, having no family history of breast cancer, and a normal previous breast screen do not require further investigation with imaging. A female with non-cyclic focal mastalgia and a strong suspicion of underlying grave pathology is a positive candidate for further investigation with an imaging modality.[11]

Breast Ultrasound[12][13]

Ultrasound uses sound waves to produce an image of the breast area being examined. Because of dense breast tissue, ultrasound is being used in patients younger than 35. However, a mammogram is recommended for further evaluation if any suspicious finding is observed on USG.

Mammogram[14][15]

It is an imaging modality that uses high-amperage, low-voltage x-rays. A female over 35 should undergo mammography if a physical exam detects a focal area of pain with unusual thickening or a breast lump. 

Breast Biopsy

Suppose imaging modalities show any abnormal finding regarding a breast lump or a focal thickening with underlying breast pain in that region. In that case, further investigation is then carried out with the help of a biopsy. During a biopsy[preferably core needle biopsy], a sample of breast tissue is taken from the area under question and sent for further histopathologic evaluation. 

Sometimes, breast imaging is done to alleviate patients' anxiety, and once they are reassured with a negative imaging result, they stop seeking further medical assistance.

Treatment / Management

In the majority of cases, general reassurance that these pain episodes are not associated with breast cancer or any other grave pathology helps alleviate patient symptoms, and they no longer seek medical assistance. However, a few, about 15% to 20%, still require treatment because of either the negative impact this disease has on their life or the increased intensity and frequency of pain episodes after the first visit.[2] The initial step in the management of such a patient is to search for the exact etiology of mastalgia and focus on alleviating their pain with conservative treatment. 

Conservative Management

Using a well-fitting sports bra:

This helps to contain and provide support to the heavy, pendulous, painful breasts during strenuous physical activities of the day. 60% to 70% of women report pain relief with the use of adequately fitted breast garments.[11][16]

Use hot and cold compresses:

This might provide relief when applied, especially during the night before sleep.

Relaxation therapy:

It helps to relieve high levels of anxiety and depression associated with mastalgia.

Dietary modification:

Reducing the intake of tea, coffee, chocolate, and carbonated soft drinks while following a low-fat diet high in vitamins and fiber has shown beneficial effects. Inculcating an exercise regime within the routine also relieves pain, as physical activity decreases estrogen release and increases its breakdown, thus proving beneficial.[17]

Using over-the-counter pain medications:

Oral or topical administration of ibuprofen or the use of acetaminophen and NSAIDs have shown promising results. However, these are temporary acute pain-managing agents,  and they should be monitored and tailored to prevent the development of serious side effects with their use in toxic amounts.

Pharmacological Management

Generally, breast pain resolves on its own in 3 to 6 months. If it doesn't, then pharmacological treatment usually provides promising results.

Topical or Oral NSAID use:

When the pain is intense, NSAIDs can provide symptomatic treatment with adequate analgesia. The best available modalities are oral NSAIDs, acetaminophen, ibuprofen, and topical (diclofenac in patch or gel form).[18](A1)

Evening Primrose Oil and vitamin E:

Literature has shown promising results with the use of these supplements. Primrose oil is documented to maintain a favorable balance of fatty acid in our cells. At the same time, using 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. However, it is recommended to stop its use if no improvement is observed after 4 to 6 months.[19][20](B3)

Prescription Medication use

Tamoxifen:

In cases of severe refractory mastalgia, tamoxifen is considered the first-line treatment, a prescription medication for breast cancer. It is administered during the luteal phase of the menstrual cycle in a low dose to avoid side effects. Treatment should be stopped after 3 to 4 months if no favorable results are obtained. Close monitoring is required as this drug is associated with side effects like headache, nausea, vaginal dryness, hot flashes, and joint pain.[21](B3)

Danazol:

The only FDA-approved drug for the treatment of mastalgia. This is also not free from side effects, which include acne, voice changes, weight gain, hot flashes, and menstrual irregularities. The majority of the patients tend to lose adherence because of such an intolerable side effect profile.[22] A thorough discussion should be conducted with the patient regarding the benefit and risk profile before starting these medications.

Differential Diagnosis

The major primary concern of females presenting with mastalgia is breast cancer. However, breast pain is 1 of the least associated symptoms of breast cancer, present only in 0.5% to 2% of patients later diagnosed with cancer. Other differentials for breast pain include pain from a previous surgical scar, chest wall pain from previous trauma, breastfeeding-associated mastitis, costochondritis, rib fracture, shingles, referred shoulder pain, or sometimes it may be a clue to other serious diseases like coronary artery disease, pleurisy or pericarditis.

Prognosis

It is complicated to predict prognosis as mastalgia presents many underlying pathological and psychological causes. However, if no underlying pathology is present, it has high spontaneous remission rates within 3 months to 3 years. Factors affecting the prognosis include the age of onset and the underlying etiology. For cyclic breast pain, 60% of patients show a successful response to therapy, but recurrence is generally seen within 2 years, while 20% to 30% show complete resolution. In non-cyclic pain, there is an inadequate response to therapy unless and until the exact underlying etiology is known and adequately treated. Still, 50% of women show spontaneous resolution.[23]

Complications

In the majority of cases, the complications seen are related to the medication used for the treatment of mastalgia. Side effects such as nausea, bloating, headache, vaginal dryness, hot flashes, leg cramps, weight gain, and menstrual irregularities are most commonly associated with pharmacological treatment modalities, likely with the use of danazol and tamoxifen. Generally, it is preferred to question the patient regarding the history of such symptoms before starting these drugs.[24]