Mastodynia

Etiology

The etiology of breast pain can be classified into three major categories: cyclic, noncyclical, and extra-mammary. Management of the pain is often determined by the categorization of the pain.[3][4][5]

Cyclical Breast Pain: more frequently manifests in patients aged from the mid-twenties to 30 years old.[6] It often presents as diffuse bilateral pain but can be more localized in some cases with a predilection for the upper outer quadrant. Cyclical breast pain is thought to be related to hormonal changes. It constitutes two-thirds of female breast pain patients, presenting most severely a week before the onset of their menstrual cycle. This corresponds with the luteal phase and often improves with the onset of menses.[3][7]

Periodic discomfort in the breasts could be considered normal because increases in estrogen levels will stimulate ductal elements. Other hormonal effects include a decrease in progesterone stimulating breast stroma and an increase of prolactin, causing stimulation of ductal secretion. All of these hormonal changes are regular events during the menstrual cycle in women of reproductive age.[8]

Cyclic mastalgia can also be associated with the use of hormonal therapy, such as oral contraceptive pills and postmenopausal hormonal therapy. Some cases have shown amelioration of pain during pregnancy, with lactation, and with the onset of menopause. Improvement in these situations corroborates the association with hormonal changes. Between twenty and thirty percent of cyclical breast pain resolves spontaneously. However, as much as sixty percent of cases will have recurring episodes.[9]

Noncyclical Breast Pain: This classification represents up to 25% of the cases of mastodynia. It affects women with true mastalgia usually aged 40 years or older, often perimenopausal. When presenting with noncyclical breast pain, it is important to first rule out any neoplastic, inflammatory, or vascular disease.[10] Noncyclical pain follows an unusual pattern, showing no relationship with the menstrual cycle. The course of pain can be intermittent or constant with spontaneous resolution in 50% of patients. The location of noncyclical pain is variable and most commonly unilateral.[9][11] There are several causes for this category of breast pain thought to relate to breast or chest wall lesions, including:[12]

• Breast cysts, causing frequent pain with an abrupt presentation.
• Stretching of Cooper ligaments because of large, pendulous breasts.
• Ductal ectasia, causing a dilatation of the duct produced by the entrance of lipid material through the duct wall causing inflammation, fever, and pain.[13]
• Mastitis or breast abscess
• Diet and lifestyle can be related to breast pain as there is some evidence of association with high consumption of fats and caffeine as well as with smoking.[14][15]
• Hormone replacement therapy in menopausal women.
• Thrombophlebitis of subcutaneous breast and chest wall veins as in Mondor disease.[10][12]

Other etiologies would fall under the extramammary pain category, such as neoplasia, pregnancy, trauma, medications (hormones, antibiotics, cardiovascular agents, and some antidepressants), and previous breast surgery, of which up to 30% of women would experience persistent noncyclic mastalgia.[10][11][12][16]

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, Tietze syndrome, among other spinal and paraspinal disorders.[10][11][17]

Epidemiology

Breast pain has been found more commonly in women 30 to 50 years of age.[9] Based on literature research, we can assume that in the US women's population, 60 to 70% will experience breast pain at some point in their lives, of which around 30% seek medical attention. Out of this last group, 20% of all cases could be considered severe.[6][14]

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.[7]

The worldwide prevalence of breast pain varies depending on the population being studied. A study was conducted on women from the UK using a survey to correlate physical activity with 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.[18] The prevalence of breast pain can vary depending on the region as well as ethnicity. Women in the UK report a 60% incidence of breast pain while women of Asian ethnicity have been found to have a breast pain prevalence of 5%.[19]

History and Physical

Obtaining a detailed history and conducting a complete clinical examination is extremely useful to reach a correct diagnosis. Likewise, the use of a pain diary for patients to recollect the behavior of pain during the episodes can provide valuable information.[20]

During the physical examination, the main focus is to emphasize the breasts and chest wall. Exploration of the chest wall facilitates differentiating extramammary pain from true mastalgia. For examination, the patient should be asked to lie on each side, allowing for the breast tissue to fall away from the chest wall and granting space for palpation of underlying chest wall muscles and the rib cage. Secondly, the breast should be elevated with one hand while the examiner palpates the underlying chest wall with the other.[17][21]

Characteristics of breast pain that strongly suggest an extramammary etiology include unilateral location, induction of pain by activity, very lateral or medial location in the breast, precipitation of chest pain by applying pressure on a specific area of the chest.

Proceeding with breast exploration, the examiner should review the four breast quadrants systematically, with the patient lying and sitting with both hands on her hips along with both hands above her head. Subareolar, supraclavicular, infraclavicular, and axillary areas should be explored as well, observing for any enlarged lymph nodes, among other different signs that could suggest breast malignancy. Some additional signs to watch out for include skin or nipple retraction, edema, change in color, dimpling, ulceration, asymmetry, scars, inflammation, or abnormal nipple discharge.[22]

If an abnormality is identified during the physical examination, it must be delineated, documented, and related to areas noted by the patient as painful. The patient should be referred for further evaluation by a specialist.

Evaluation

After a meticulous clinical history and physical examination, physicians should use their clinical judgment to determine the need for further imaging or laboratory evaluation.

Breast pain is most commonly evaluated by the use of mammography and breast ultrasound. Women with abnormal physical exam findings such as skin changes, mass, or bloody nipple discharge are considered for mammography and/or breast ultrasound. The primary aim of this testing, at least initially, is for the exclusion of a breast cancer diagnosis.[23] On the other hand, women who present with breast pain, but have no suspicious findings on physical exam, should undergo evaluative breast imaging. This imaging should be ordered in accordance with the recommendations of The American College of Radiology Appropriateness Criteria based on patient age and pain characteristics.[24] 

It is proposed that imaging is not required for patients with bilateral, non-focal, or cyclical mastalgia, as long as the patient is up to date with regular breast cancer screenings. This recommendation stems from the fact that there is a low likelihood of finding the specific cause of pain with imaging. However, patients with unilateral, noncyclical, or focal mastalgia, for whom an extramammary etiology (as chest wall pain) has been excluded, should undergo breast imaging to identify the underlying etiology and to exclude breast cancer. Up to this point, the choice between mammography or ultrasound was based on age:

Women Under 30 Years: Ultrasound is the first choice given its accuracy. However, mammography should be suggested if there is a suspicious finding on the ultrasound or the patient has a family history of premenopausal breast cancer.[25] 

Women Aged 30-39 Years: Ultrasound with a recommendation of unilateral or bilateral mammography is recommended. This recommendation is based on the fact that there is strong evidence in the literature of small cancers found at the referred site of pain identified by mammography but not by ultrasound.[26]

Women Aged 40 and Older: They should always undergo mammography and ultrasound.[27]

In many cases, breast imaging is very helpful for alleviating the patient’s anxiety. However, once they are reassured by negative breast imaging results, they often stop seeking further medical attention.[28][29][30]

Treatment / Management

Up to 85% of women with mastodynia, will show alleviation of pain episodes after getting reassurance of not having breast cancer. The remaining 15% will require treatment apart from reassurance, mainly because of negative impact physical activity (30%), sexual activity (up to 40%) as well as their life quality in work and social activities (10%).[6][7][11]

The most important steps for the physician are to rule out the diagnosis of breast cancer, find the correct etiology of mastalgia, and focus pain treatment according to the possible cause. The first-line pain-relieving therapy should be conservative and given a trial of at least six months before moving to second-line therapy.

General Treatment Measures

• Improving physical support of the breast with the use of supportive garments, such as a well-fitted brassiere. Women with large breasts would benefit from a soft, supportive garment that reduces the stretching of the Cooper ligament. Literature shows that approximately 70% of women wear an incorrect size of supportive breast garment.[31]

• The use of relaxation therapy can help patients manage their breast pain. One example is evening primrose oil (EPO), which contains the fatty acid gamma-linolenic acid, a precursor of prostaglandin E1. Though its mechanism is not clear, such therapies are generally found harmless, and some physicians endorse their use if it provides relief for patients.[8][32]
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• Dietary recommendations, such as reducing the consumption of methylxanthines found in beverages like coffee, chocolate, tea, and some soft drinks.[33] Also recommended is a reduction in the consumption of saturated fatty acids and an increase in the consumption of unsaturated fatty acids.[8] In some patients, the concomitant inclusion of an exercise routine could improve mastalgia as a result of the release of endorphins.[31]

• Nonsteroidal anti-inflammatory drugs (NSAID) & acetaminophen, in some studies, are effective in up to 80% of women with mastodynia while having minimal side effects. They can be administered orally or topical (e.g., ibuprofen or diclofenac in patch or gel form).[34]
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Pharmacological Therapy

It would be used in patients that have persistent breast pain after 6 months of using first-line therapy. The preferred medications are:

• Tamoxifen: This is usually the first choice for treatment, especially in patients with severe refractory mastalgia. Recommended effective doses for use are 10-20 mg daily. This dosage presents with fewer side effects when administered to women during the luteal phase of the menstrual cycle and at the lower dose. Some of the side effects could be vaginal dryness, hot flashes, an increase in the risk of blood clots, cataracts, strokes, joint pain, and leg cramps.[5][17][35][36] Patients should be questioned regarding an increased risk for some of these conditions before initiating this medication.
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• Danazol: This is the only US Food and Drug Administration (FDA) approved medication to treat mastalgia. The recommended dose is 200mg daily administered during the luteal phase of the menstrual cycle. This dosing regimen helps to optimize the effectiveness of the medication and reduces the odds of presenting with side effects such as menstrual irregularity, weight gain, hot flashes, and deepening of the voice.[34][37]
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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.[1]

Postmenopausal women presenting with mastodynia and using hormone-based medications should decrease or cease these medications. There should be a thorough discussion with the patient regarding the risks and benefits of decreasing or removing these hormone-based therapies in the setting of mastodynia.[38]

Differential Diagnosis

The primary differential of concern for patients presenting with mastodynia is breast cancer, although an extremely low percentage of patients with breast pain will be diagnosed with this condition. The rates of cancer among patients with breast pain fluctuate from 0.5% to 3.3%. While it is a less common cause of breast pain, the concern of this diagnosis is one of the main causes for women to seek medical attention.[11][19][29] Prior breast surgery could lead to pain originating from adherent scar tissue on the chest wall, demonstrating the importance of a well-conducted clinical history when first evaluating the patient. Other differential diagnoses to rule out include chest pains originating in extramammary areas, such as intercostal neuralgia and pain from cardiac discomfort.[4]

Prognosis

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.[39] 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.[9]

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.[9][10]

Furthermore, since mastodynia is a symptom with a multitude of underlying causes, the prognosis often relates to the etiology that is discovered.

Complications

Taking into account that there are so many potential etiologies for mastalgia, any pain complications that a patient might present with often depend on the underlying etiology of pain. However, in many cases, patients show no complications other than physical discomfort.[40]

Some patients may show complications related to the medications used to treat mastalgia. For example, side effects of headaches and nausea have been reported after the use of bromocryptine and danazol, while oral contraceptive pills can result in menorrhagia, nausea, and headaches.[41]