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Address reprint requests and correspondence to Robin L. Smith, MD, Division of General Internal Medicine, Mayo Clinic College of Medicine, 200 First St SW, Rochester, MN 55905
Affiliations
Breast Diagnostic Clinic, Division of General Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minn.
Pain is one of the most common breast symptoms experienced by women. It can be severe enough to interfere with usual daily activities, but the etiology and optimal treatment remain undefined. Breast pain is typically approached according to its classification as cyclic mastalgia, noncyclic mastalgia, and extramammary (nonbreast) pain. Cyclic mastalgia is breast pain that has a clear relationship to the menstrual cycle. Noncyclic mastalgia may be constant or intermittent but is not associated with the menstrual cycle and often occurs after menopause. Extramammary pain arises from the chest wall or other sources and is interpreted as having a cause within the breast. The risk of cancer in a woman presenting with breast pain as her only symptom is extremely low. After appropriate clinical evaluation, most patients with breast pain respond favorably to a combination of reassurance and nonpharmacological measures. The medications danazol, tamoxifen, and bromocriptine are effective; however, the potentially serious adverse effects of these medications limit their use to selected patients with severe, sustained breast pain. The status of other therapeutic strategies and directions for future research are discussed.
Mastalgia, or breast pain, was described in the medical literature as early as 1829
Pain is one of the most common breast disorders experienced by women. In the United Kingdom, breast pain vies with palpable mass as the symptom described most frequently by women presenting to general practitioners or seeking consultation in specialty breast clinics.
In a large cohort of 2400 women enrolled in a health maintenance organization in the United States during a 10-year period, pain was the most common breast symptom, prompting medical evaluation and accounting for 47% of breast-related visits.
Similarly, in a study of 1171 women attending an obstetrics-gynecology clinic in the United States, 69% experienced regular premenstrual breast discomfort, and 11% had moderate to severe breast pain more than 7 days per month.
may prompt more women to seek medical attention for breast symptoms, mastalgia generally is underreported. In a survey of working women in South Wales, 45% described mild breast pain, and 21% described severe breast pain, but fewer than half of the women with severe pain had reported this symptom to a physician.
Breast pain is uncommon in men, although pain and tenderness may occur in men who develop gynecomastia secondary to medications, hormonal imbalance, cirrhosis, or other conditions.
The evaluation of breast pain varies according to its assignment within the 3 broad classifications of cyclic mastalgia, noncyclic mastalgia, and extramammary (non-breast) pain.
Cyclic mastalgia, by definition, occurs in premenopausal women and connotes breast pain that is clearly related to the menstrual cycle. Noncyclic mastalgia is defined as constant or intermittent breast pain that is not associated with the menstrual cycle. Extramammary pain from various sources may present with symptoms of breast pain. Cyclic mastalgia accounts for approximately two thirds of breast pain in specialty clinics, whereas noncyclic mastalgia accounts for the remaining one third.
Mastalgia is a common and enigmatic condition; the cause and optimal treatment are still inadequately defined. Mastalgia may be severe enough to interfere with usual daily activities, and its effect on quality of life often is underestimated.
We review the literature regarding the potential etiology, clinical evaluation, and treatment of mastalgia to assist the clinician caring for women with breast pain. Articles selected were obtained from a MEDLINE search and from bibliographies and include all relevant studies, clinical trials, published clinical experience, and recent reviews available in the English language.
CYCLIC MASTALGIA
Minor breast discomfort and swelling within the few days before onset of menses is considered a normal physiological occurrence. In order of decreasing frequency, premenstrual breast symptoms reported by women are tenderness, swelling, pain, and lumpiness.
Women who experience more severe and prolonged pain are considered to have cyclic mastalgia. Research criteria for the diagnosis of cyclic mastalgia are (1) pain severity greater than 4.0 cm measured on a 10.0-cm visual analog scale and (2) pain duration of at least 7 days per month.
Applying this threshold in a clinic-based study in the United States, approximately 11% of premenopausal women could be diagnosed as having cyclic mastalgia. However, an additional 9% of premenopausal women experienced breast pain of severity greater than 4.0 cm on the visual analog scale for 5 to 6 days per month.
Cyclic breast pain usually starts during the luteal phase of the menstrual cycle and increases in intensity until onset of menses, when it dissipates. Some pain may be present to a lesser degree during the entire cycle with premenstrual intensification of symptoms. The pain typically involves the upper outer breast area and radiates to the upper arm and axilla. Most cyclic mastalgia is diffuse and bilateral but may be more severe in one breast. Patients often describe the pain as “dull,” “heavy,” or “aching.”
The consequences of cyclic mastalgia are not trivial. In a large clinic-based sample of women, symptoms interfered with sleep in 10%; with work, school, and social functioning in 6% to 13%; with physical activity in 36%; and with sexual activity in 48% of women whose symptoms met the criteria for cyclic mastalgia.
In addition, women whose symptoms meet the criteria have different breast-related health behaviors. They are more likely to undergo mammography before age 35 years, engage in self-treatment of breast pain, consult a physician regarding other breast concerns, and undergo breast biopsies than symptomatic women whose symptoms do not meet the diagnostic criteria for cyclic mastalgia or asymptomatic women.
The symptoms tend to persist with a relapsing course. Remission often occurs with hormonal events such as pregnancy or menopause. Only 14% of women with cyclic mastalgia experience spontaneous resolution; however, 42% experience resolution at menopause.
Despite extensive studies done to identify causative histopathological, hormonal, nutritional, or psychiatric abnormalities, few consistent findings have been uncovered, and the etiology of cyclic mastalgia is unknown.
Histological Associations.—For many years, the clinical manifestations of breast pain, tenderness, and nodularity were considered synonymous with fibrocystic histology of the breast. Accordingly, clinical evaluation of breast pain was directed toward identifying underlying histopathological diagnoses.
However, the association between breast pain and fibrocystic histology has been inconsistent. In one study, the fibrocystic histological findings of intraductal proliferation, adenosis, sclerosing adenosis, papillomatosis, duct ectasia, intraductal debris, apocrine metaplasia, microcysts, and proliferative periductal connective tissue were common but did not differ among groups with cyclic breast pain, noncyclic pain, and no symptoms.
In a study of 39 women with cyclic breast pain who underwent breast biopsy, all had fibrocystic histological changes. These findings were also present in 61 of 68 women without breast pain who underwent biopsy for other reasons.
Thus, fibrocystic changes of the breast comprise various histological findings in both asymptomatic and symptomatic women. Except for proliferative change or atypia, which confers an increased risk of breast cancer,
The designation “fibrocystic” remains popular because it encompasses the common clinical findings of breast pain, tenderness, and nodularity; however, it emphasizes potential histopathological correlates. For women with mastalgia, it may be more helpful to distinguish the symptom of pain in planning evaluation and treatment.
Recently, the potential role of inflammation and inflammatory cytokines in mastalgia was studied. No differences were found between 29 premenopausal women with breast pain and 29 matched asymptomatic women regarding the degree of inflammatory cell infiltration and cytokine expression (interleukin 6 and tumor necrosis factor α) in breast tissue specimens.
Hormonal Associations.—That hormonal factors have a role in cyclic mastalgia is intuitive because this condition is defined by its relationship to the menstrual cycle and its tendency to change during pregnancy, menopause, and hormone therapy.
Nonetheless, consistent hormonal abnormalities have not been identified. Several hormonal imbalances with potential causative roles in cyclic mastalgia have been investigated, and each has findings in support and opposition (Table 1
Increased release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) during stimulation with thyrotropin and gonadotropin-releasing hormones in subjects with cyclic mastalgia compared with asymptomatic controls.
Increased release of prolactin during stimulation with thyrotropin and gonadotropin-releasing hormones in subjects with cyclic mastalgia compared with asymptomatic controls.
Hypothesis from studies assessing change in essential and saturated fatty acid levels in subjects with cyclic mastalgia compared with asymptomatic controls, suggesting effects on prostaglandins and receptor sensitivity to normal circulating hormones. 55,57
* Excess and deficiency refer to luteal-phase hormone levels in subjects with cyclic mastalgia compared with asymptomatic controls.
† Increased release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) during stimulation with thyrotropin and gonadotropin-releasing hormones in subjects with cyclic mastalgia compared with asymptomatic controls.
‡ Increased release of prolactin during stimulation with thyrotropin and gonadotropin-releasing hormones in subjects with cyclic mastalgia compared with asymptomatic controls.
§ Hypothesis from studies assessing change in essential and saturated fatty acid levels in subjects with cyclic mastalgia compared with asymptomatic controls, suggesting effects on prostaglandins and receptor sensitivity to normal circulating hormones.
Few recent investigations have examined hormonal causation in cyclic breast pain. The inconsistent findings of prior studies may be due to differences in patient selection, sampling methods, and circadian and cyclic variations in hormone levels. Thus, a definitive causal hormonal abnormality has not been identified.
Fluid-Electrolyte Balance and Nutritional Associations.—Premenstrual breast swelling is associated with mastalgia and has been considered a possible etiologic factor. Some investigators posit that shifts in the water-electrolyte balance in nonlactating breasts related to prolactin lead to cyclic painful swelling of breast microcysts.
and methylxanthine effects. Reductions in dietary fat or caffeine consumption are frequently proposed as therapeutic options for mastalgia.
Psychological Associations.—The potential psychological origin of breast pain has been explored throughout the medical literature. In 1829, Sir Astley Cooper
wrote that women seeking advice for breast pain usually had “a nervous and irritable temperament.” Although endocrine and neuralgic aspects of breast pain were also considered, similar views of the psychological element predominated for many years.
that found that women with mastalgia and a control group of women with varicose veins had similar measures of anxiety, phobia, obsessionalism, and somatic anxiety. Women with varicose veins had higher scores for depression (P<.01) and hysteria (P<.001).
among women with breast pain compared with asymptomatic women. Comparable clinical levels of emotional distress have been reported in women with severe mastalgia and women with breast cancer undergoing surgical treatment.
In another recent study, women with breast pain had increased anxiety, depression, somatization, and history of emotional abuse compared with women with breast lumps alone.
Women with breast pain may experience greater cyclic fluctuation in anxiety and depression. In a study of 20 women with cyclic breast pain, levels of anxiety and depression were higher and changes in anxiety and depression scores were greater between the follicular and luteal phases than in 12 asymptomatic women.
The extent to which psychological distress has a causal or consequential relationship to breast pain is unclear; however, substantial improvements in depression and social impairment were noted in women whose pain was treated successfully.
Cyclic breast pain and tenderness are part of the premenstrual syndrome and are among the constellation of physical symptoms associated with the premenstrual dysphoric disorder.
The relationship between cyclic mastalgia and other premenstrual symptoms has been studied. Luteal-phase symptoms, including water retention, negative affect, impaired concentration, and behavior change, were significantly greater in women with severe cyclic mastopathy compared with women without breast symptoms. Also, women with severe cyclic mastalgia experienced more breast symptoms and negative affect in the follicular phase of the menstrual cycle.
Similarly, a study of 30 subjects showed that most women whose symptoms meet the criteria for cyclic mastalgia experienced other premenstrual and somatic symptoms as measured by a menstrual symptom severity list (Figure 1). However, 12% of these women had few other premenstrual symptoms.
In a follow-up study, investigators found that, although premenstrual symptoms were common in women with cyclic breast pain, only 16% of women had sufficient symptoms that met the criteria for both cyclic mastalgia and premenstrual syndrome.
Figure 1Timeline of subjects with cyclic mastalgia. High level (top) and low level (bottom) of other premenstrual symptoms. Mastalgia was measured with a 10-cm visual analog scale; other menstrual symptoms were measured with a 100-point menstrual severity scale. From Tavaf-Motamen et al,
Although breast cancer is not considered a cause of cyclic breast pain, a few studies have identified a potential association between cyclic mastalgia and breast cancer risk. In a case-control study, scores for premenstrual tenderness involving the unaffected breast were higher in 192 premenopausal women with early-stage breast cancer than in 192 age-matched premenopausal women without breast cancer. After adjustment for other risk factors, the odds ratio for breast cancer was 1.35 (95% confidence interval, 1.01–1.83) for women with any cyclic pain and 3.32 for women with severe symptoms.
This finding of an association between cyclic mastalgia and breast cancer risk is consistent with another study of retrospectively reported cyclic breast symptoms in premenopausal women with and without a history of breast cancer.
It has been hypothesized that increased tissue sensitivity to estrogen, perhaps related to dietary fat intake and fatty acid levels, has an etiologic role in both cyclic breast pain and breast cancer risk and may account for the relationship.
However, reporting of breast symptoms by premenopausal women with breast cancer may be amplified, generating a bias and alternative explanation for these observations.
NONCYCLIC MASTALGIA
Noncyclic mastalgia involves constant or intermittent pain that is not associated with the menstrual cycle. Less common than cyclic mastalgia, it accounts for approximately 31% of women seen in mastalgia clinics.
Noncyclic mastalgia tends to be unilateral and localized within a quadrant of the breast; however, diffusely distributed pain and radiation to the axilla also occur.
Many women are postmenopausal at onset of symptoms.
Etiology
Noncyclic breast pain may result from pregnancy, mastitis, trauma, thrombophlebitis, macrocysts, benign tumors, or cancer; however, only a minority of breast pain is explained by these conditions. Most noncyclic breast pain arises for unknown reasons, yet it is believed more likely to have an anatomical, rather than hormonal, cause. An exception may be breast pain that is associated with medication use (Table 2).
Table 2Medications Associated With Breast Pain in Women
Medications causing galactorrhea and gynecomastia and believed to be associated with breast pain. Other medications (not listed) also may be associated with breast pain and should be considered according to clinical circumstances.
Medications causing galactorrhea and gynecomastia and believed to be associated with breast pain. Other medications (not listed) also may be associated with breast pain and should be considered according to clinical circumstances.
Medications causing galactorrhea and gynecomastia and believed to be associated with breast pain. Other medications (not listed) also may be associated with breast pain and should be considered according to clinical circumstances.
Medications causing galactorrhea and gynecomastia and believed to be associated with breast pain. Other medications (not listed) also may be associated with breast pain and should be considered according to clinical circumstances.
Medications causing galactorrhea and gynecomastia and believed to be associated with breast pain. Other medications (not listed) also may be associated with breast pain and should be considered according to clinical circumstances.
Medications causing galactorrhea and gynecomastia and believed to be associated with breast pain. Other medications (not listed) also may be associated with breast pain and should be considered according to clinical circumstances.
Medications causing galactorrhea and gynecomastia and believed to be associated with breast pain. Other medications (not listed) also may be associated with breast pain and should be considered according to clinical circumstances.
Medications causing galactorrhea and gynecomastia and believed to be associated with breast pain. Other medications (not listed) also may be associated with breast pain and should be considered according to clinical circumstances.
Medications causing galactorrhea and gynecomastia and believed to be associated with breast pain. Other medications (not listed) also may be associated with breast pain and should be considered according to clinical circumstances.
Carboprost, dinoprostone (and other prostaglandins)
Estramustine
* Information obtained from MEDLINE, MICROMEDEX, and discussion with breast specialists and pharmacists.
† Medications causing galactorrhea and gynecomastia and believed to be associated with breast pain. Other medications (not listed) also may be associated with breast pain and should be considered according to clinical circumstances.
Unilateral, noncyclic breast pain may result from exogenous estrogen exposure. Interestingly, in one study, 12 of 33 women developed breast pain within 1 year of initiation of menopausal hormone therapy. Of the 33 women, 7 women with moderate to severe pain experienced an increase in mammographic breast density, 5 women with mild to moderate pain had no increase in breast density, and 2 of 21 women without pain had an increase in breast density (P=.005).
; however, the association between breast pain or tenderness and change in mammographic density during different hormonal treatments requires confirmation.
Comparatively, the selective estrogen receptor modulators, tibolone and raloxifene, have much lower rates of associated breast pain.
Recently, the possibility of a relationship between duct ectasia (dilatation of the milk ducts) and noncyclic breast pain was explored. Ultrasonographic measurement of ductal diameter differs between asymptomatic women and women with cyclic and noncyclic breast pain. The maximum mean width of the milk ducts was 1.8 mm in asymptomatic women, 2.34 mm in women with cyclic mastalgia, and 3.89 mm in women with noncyclic mastalgia (P<.001). Ductal width correlated with pain intensity.
The occurrence of subclinical breast cancer in women with focal, noncyclic breast pain who present to breast or oncology clinics has been studied (Table 3
Conversely, in a review of 1532 women with breast pain incidental to presenting complaint, the risk of breast cancer was decreased in women having pain, with an adjusted odds ratio of 0.63 (95% confidence interval, 0.49–0.79). Women with breast pain as a sole complaint were excluded.
In a recent case-control study of women referred for diagnostic breast imaging to evaluate pain, there were no differences between the mammographic findings and frequency of malignancy in women with pain compared with a matched control group undergoing routine screening.
In a review of patients presenting to a breast clinic with focal breast pain as primary symptom, pain was the only symptom in 17 of 36 subjects with breast cancer
In a review of 460 patients presenting to a breast clinic, 209 had focal pain as primary symptom; of 8 with breast cancer, pain was the only symptom in 1, a mass was present in 7, and nipple retraction was present in 3
In a retrospective cohort study of 2400 women (aged 40-69 y) presenting to health maintenance organizations over 10 years, unilateral pain was reported by 91% and bilateral pain by 9%
In a review of 2879 patients with breast symptoms, 1141 had breast pain as primary symptom; the relative risk of breast cancer in patients aged 41 to 55 years with breast pain compared with those presenting without breast symptoms was 0.6 (95% confidence interval, 0.4-1.1)
The incidence of pain relating to prior breast surgery appears to be high. In a retrospective survey of 282 women at least 1 year after breast surgery, the incidence of breast pain after mastectomy, mastectomy with reconstruction, augmentation, and reduction was 31%, 49%, 38%, and 22%, respectively. For analysis, women undergoing lumpectomy and axillary lymph node dissection were included in the group who had undergone mastectomy. The use of breast implants for reconstruction and the submuscular placement of implants for augmentation were associated with increased pain. Breast pain did not differ on the basis of silicone vs saline implants.
Proposed causes for postsurgical breast pain vary with the procedure and include dysesthetic scar pain, nerve regeneration, and focal nerve injury due to ischemia, radiation therapy, lymphedema, and implant capsule formation.
Ipsilateral axillary and arm pain also may result from injury to the intercostobrachial nerve (injured in 80%-100% of patients undergoing axillary dissection), brachial plexopathy secondary to radiation therapy, implant compression, complex regional pain syndrome, and referred pain.
Postmastectomy pain syndrome describes pain resulting from surgical treatment of breast cancer, including pain resulting from breast surgery (lumpectomy or mastectomy), axillary dissection, and phantom symptoms.
Phantom breast syndrome is a sensation of persistence of the breast after mastectomy. Phantom breast pain can be distinguished from pain related to scarring and occurs in 12% of women interviewed 1 year after mastectomy.
Phantom breast pain is associated with preoperative pain and is believed to arise when constant painful sensory input establishes a durable sensory pattern in the brain.
Extramammary pain due to various conditions may present as breast pain. The differential diagnosis for mastalgia is extensive (Table 4); however, the causes most commonly encountered in the evaluation of breast pain are costochondritis and other chest wall syndromes.
Distinguishing between pain localized to the breast or chest wall or radiating from elsewhere is usually straightforward, although diagnosis of patients with inconsistent findings or more than 1 source of pain is more challenging. Establishing the diagnosis allows for appropriate, economical evaluation and management and minimizes unnecessary patient concern.
Chest wall syndromes comprise a group of conditions causing musculoskeletal chest pain, including costochondritis, Tietze syndrome, slipping and clicking ribs, and arthritis, which may be nontraumatic and insidious at onset.
Costochondritis is characterized by pain and tenderness of the costochondral or chondrosternal joints, with involvement of the second through fifth costal cartilages.
Tietze syndrome presents with similar symptoms but also has nonsuppurative swelling of the cartilaginous articulations and particular involvement of the second and third costochondral junctions.
Many researchers advocate use of a localized diagnostic and therapeutic injection with an anesthetic and corticosteroid to the affected site in selected patients, noting a favorable response rate and few adverse effects.
Other causes of extramammary pain occur less frequently but should be considered when evaluating the patient presenting with breast pain.
CLINICAL EVALUATION
History
Obtaining a patient's history should be directed toward identifying and characterizing breast-related symptoms. Historical features of breast pain to elicit include its quality and location, relationship to physical activity, and severity as manifested by interference with usual activities. Other breast symptoms, such as associated mass, inflammation, or nipple discharge, should be noted. Potential hormonal influences should be assessed, including the relationship to the menstrual cycle, pregnancy, contraceptive use, and hormonal therapies. Reviewing the patient's medications to identify any associated with breast pain may be helpful. The history also allows additional symptoms or information to be obtained that would suggest a nonbreast source of pain. Risk assessment for breast cancer should include obtaining the appropriate reproductive, medical, and family history.
Physical Examination
Clinical breast examination requires careful inspection and palpation of each breast, nipple-areolar complex, and regional lymph nodes. Detection of localized, generalized, or bilateral breast tenderness may be helpful. Examination with the patient seated, supine, or lateral decubitus with the breast falling away from the chest wall may allow breast and chest wall tenderness to be distinguished.
Abnormalities detected during clinical breast examination (including a mass, asymmetry, nipple discharge, or inflammatory change) should have precedence and merit prompt evaluation. As appropriate, examination of the cervical and thoracic spine, chest wall, shoulders, upper extremities, heart, lungs, and abdomen may identify other potential causes of the pain and provide direction for diagnostic evaluation.
Diagnostic Studies
Mammography is often used to evaluate breast pain; however, the yield is low in the setting of normal findings on clinical examination. In one study, approximately 36 of 240 women with newly diagnosed breast cancer had localized breast pain as a presenting symptom. Of these, 10 women (28%) had normal mammographic findings and were later diagnosed as having subclinical breast cancer at the site of pain.
Conversely, in a recent case-control study, there were no differences in the incidence of malignancy among the painful breasts of women referred for mammography to evaluate the pain (0.5%), the contralateral nonpainful breasts of the same women (0.5%), and the breasts of women without pain referred for routine screening (0.7%).
Accordingly, it has been questioned whether breast pain is related to cancer or whether this symptom prompts an evaluation in which an asymptomatic cancer is identified.
In a study of 110 directed ultrasonographic examinations performed for focal breast pain, no breast cancer was found, and a benign finding at the site of pain was identified in 18 women. Although these results were reassuring, the women were relatively young, and most had no family history of breast cancer, limiting generalization from this low-risk group.
Breast imaging should be tailored to the age of the patient, risk for breast cancer, and other aspects of the clinical presentation.
Young women with cyclic breast pain do not require a mammogram in the absence of focal pain, suspicious findings, or risk factors. A mammogram should be considered in women with focal breast pain who are aged 30 to 35 years or older, have a family history of early breast cancer, or have other risk factors for breast cancer. Ultrasonography should be considered for focal breast pain in women of any age.
Laboratory studies are generally not useful; however, a pregnancy test must be considered in women of reproductive age if the history or examination suggests pregnancy. Other hormone levels (such as estrogen, progesterone, and prolactin) are typically within the normal range in women with breast pain; therefore, testing is unnecessary.
BREAST PAIN ASSESSMENT
Quantifying breast pain may be difficult because of its variability.
Women may note that symptoms wax and wane without provocation, with certain activities, or with the menstrual cycle. Assessment with use of a pain-rating instrument such as a visual analog scale may be helpful in initially evaluating breast pain, for making decisions regarding treatment, and for monitoring response to therapy. Prospective assessment with a daily breast pain diary to document the occurrence and severity of pain, aggravating and alleviating factors, use of medications, and interference with lifestyle is helpful for women considering treatment. These measures are particularly important for cyclic mastalgia because diagnosis based on recall of symptoms is only 65% sensitive, and diagnosis based on the prospective breast pain diary is 69% specific.
In one study, in which a modified version of the McGill Pain Questionnaire (SF-MPQ) was administered to 271 women with cyclic or noncyclic breast pain, the mean painrating index was 12.0 of 45 (similar to pain ratings in rheumatoid arthritis and cancer). The total breast pain score was most efficiently estimated by a combination of a visual analog scale, present pain index, and quality-of-life questions.
At a minimum, the patient's description of her symptoms and their effect on usual activities, a simple quantitative assessment of the pain, and decisions regarding any evaluation, follow-up, or therapeutic intervention should be documented during encounters for breast pain.
BREAST PAIN MANAGEMENT
Breast pain prompts many women to seek medical attention because of concerns about cancer.
The risk of subsequent occult malignancy after normal findings on clinical and mammographic evaluation for breast pain is estimated to be only 0.5%, making reassurance in this setting appropriate.
In clinical practice, 78% to 85% of symptomatic women are reassured after normal findings on evaluation and do not want specific intervention to alleviate the breast pain.
There is overlap between the initial therapeutic approaches for patients with cyclic and noncyclic mastalgia; however, response to intervention varies.
Hormonally active medications are more effective for patients with cyclic mastalgia and are indicated only for patients with severe, prolonged symptoms.
Numerous difficulties arise when reviewing the effectiveness of therapies for breast pain because the pain is subjective, cyclic, or fluctuating in severity and is occasionally self-limited. These characteristics make assessment of response to an intervention challenging. Additionally, the definition of a therapeutic response differs between studies, and there is a placebo effect of at least 20% (range, 10%-40%).
A wide variety of nonpharmacological measures are used to treat breast pain with little or no scientific support. Although applying evidence-based criteria to determine the studies to include for review would be more rigorous, use of this approach would exclude many interesting older studies and published clinical experience that warrant discussion. Instead, we have been more inclusive but have qualified the studies to guide clinicians and define areas for future research.
Nonpharmacological Interventions
Nonpharmacological interventions to improve breast pain are appropriate for women experiencing either cyclic or noncyclic mastalgia.
Although there has been little scientific investigation into the effectiveness of these interventions, they frequently improve breast pain in clinical practice and are of low risk and expense to the patient.
Physical Measures.—Improved mechanical support may relieve breast pain. An estimated 70% of women wear an improperly fitted brassiere.
Symptomatic women may benefit from counseling regarding proper selection and fitting of a brassiere, wearing a soft supportive brassiere during sleep, and use of a “sports bra” during exercise. Although this advice is ubiquitous as a recommendation for women with breast pain or discomfort,
there are surprisingly few clinical investigations into its utility. In 1976, a study of this intervention enrolled 114 women whose breast pain lasted more than 7 days each menstrual cycle, interfered with daily activities or sleep, and was severe enough that the women desired treatment. Subjects were fitted with a comfortable brassiere by a trained nurse, provided with 2 brassieres, and monitored every 3 months for 6 to 18 months. One hundred subjects completed follow-up, of whom 26 experienced complete relief, 49 had improvement, 21 derived no benefit, and 4 became worse. Interestingly, 11 of 15 patients who had required medication for breast pain experienced improvement or relief with this intervention.
In recent work, breast motion was assessed in 3 women during running, jogging, aerobics marching, and walking as they wore 4 different types of breast support. As expected, a sports bra provided the greatest support with regard to decreased amplitude of movement, deceleration forces, and discomfort of the breast.
Although there are numerous limitations in these uncontrolled studies, they lend credence to the widely held clinical impression that a properly fitted brassiere has therapeutic value for symptomatic women, including some in whom other treatments had failed.
The application of heat (eg, warm compresses) or cold (eg, ice packs) and gentle massage may reduce pain, particularly when symptoms are cyclic or intermittent and of short duration. Measures such as ultrasonography and acupuncture are used occasionally and are undergoing preliminary investigation for breast pain
Approximately 61% of women who listened daily for 4 weeks to an audiocassette of progressive muscular relaxation experienced substantial or complete relief of breast pain compared with 25% of control subjects who did not use the audiocassettes (P<.05). Subjects who performed relaxation techniques also had substantially more pain-free days and less anxiety than controls.
Dietary Change, Methylxanthine Restriction, and Nutritional Supplements. Dietary Fat.—The effectiveness of dietary interventions to reduce breast pain remains to be established
; however, several have shown promise. A low-fat diet was associated with a substantial improvement in mastalgia symptoms when 21 patients with severe mastopathy were randomized to a diet containing 15% fat intake or a general diet containing 36% fat intake. The subjects were monitored with symptom logs and breast examinations for 6 months, at which time 9 of 10 subjects (90%) who followed the low-fat diet and 2 of 9 controls (22%) had decreased breast symptoms (P=.0023). In the intervention group, body weight and cholesterol level were reduced, the latter associated with the decrease in symptoms.
Methylxanthine Restriction.—Although many women report that caffeine reduction or elimination alleviates their breast pain, clinical studies have not shown consistent findings. In an uncontrolled study, 61% of women with breast pain who substantially decreased caffeine intake for 1 year had decreased pain or complete relief.
However, most work in this area has focused on the relationship between methylxanthines and other aspects of fibrocystic change, including nodularity and cyst formation. In this context, little evidence supports an association between caffeine and fibrocystic breast disease.
Early proponents of the relationship between fibrocystic breast change and methylxanthines reported resolved, improved, and unchanged fibrocystic nodularity in 82%, 15%, and 2% of 45 women, respectively, who completely abstained from caffeine in an uncontrolled trial.
In a randomized trial, a statistically significant improvement in premenstrual palpable nodularity of the breast was identified in subjects who restricted caffeine compared with controls who received no dietary advice. However, the absolute change was minor, and it was concluded that the intervention had limited effectiveness for fibrocystic nodularity of the breast. These authors observed, but did not measure, an improvement in premenstrual breast discomfort during the study.
Measuring the effect of caffeine restriction on fibrocystic breast disease: the role of graphic stress telethermometry as an objective monitor of disease.
In contrast, a single-blind randomized trial of decreased caffeine consumption in 56 women showed no differences in breast pain or tenderness among those following a caffeine-free diet, a low-cholesterol diet, or an unrestricted diet.
Other investigators have found no association between caffeine and fibrocystic change of the breast, with many of the studies assessing histological change, not breast symptoms.
The nonendocrine mechanism by which methylxanthines are believed to influence fibrocystic change in the breast relates to their mediation of elevated 3',5'-cyclic adenosine monophosphate (cAMP) in fibrocystic tissue specimens and circulating catecholamines.
High caffeine intake also may be associated with altered hormone levels in postmenopausal women, with increased plasma estrone, sex hormone-binding globulin, and decreased testosterone.
Overall, no consistent evidence supports women restricting caffeine to improve physical examination, mammographic, or histological findings. Completely eliminating methylxanthines from the diet is difficult, even in clinical trials, which may mask the effectiveness of this intervention. On the basis of the few studies with breast pain as a discrete outcome,
Measuring the effect of caffeine restriction on fibrocystic breast disease: the role of graphic stress telethermometry as an objective monitor of disease.
it may be reasonable to consider this intervention in women with problematic breast pain who have moderate to heavy caffeine consumption. However, because of the nature of the studies and conflicting results, the possibility that improvement is solely due to placebo effect cannot be excluded.
Vitamins.—Several vitamins have been evaluated as potential treatments for breast pain, including vitamins B1, B6, and E.
Of these, vitamin E is used most commonly for breast pain. Early studies with small numbers of patients suggested a potential beneficial effect of vitamin E (α-tocopherol) in fibrocystic breast disease.
Proposed mechanisms include its potential to alter steroidal hormone production (dehydroepiandrosterone or progesterone), to correct abnormal serum cholesterol-lipoprotein distribution, and to function as an antioxidant.
Subsequently, a few small randomized, double-blind, placebo-controlled studies have shown no differences in breast pain using dosages of 150 to 600 IU of vitamin E per day.
Additionally, mean serum concentrations of estradiol, progesterone, testosterone, and dehydroepiandrosterone did not differ between vitamin E- and placebotreated women.
Many practitioners continue to recommend vitamin E for breast pain, although uncertain of whether the relatively low doses and short duration of treatment in these trials exclude a beneficial effect. Small studies of vitamins B1 and B6 showed no benefit compared with placebo for the treatment of cyclic breast pain.
Evening Primrose Oil.—For women with cyclic breast pain who elect treatment, evening primrose oil (gammalinolenic acid) has been widely advocated as an initial option.
Also, several researchers have reported favorable response and adverse effect rates for evening primrose oil from sequential uncontrolled studies and clinical series.
used a randomized, double-blind factorial design to evaluate evening primrose oil and fish oil for premenopausal women with chronic, severe cyclic or noncyclic mastalgia. Women were randomized into 4 groups: fish oil and control oil, evening primrose oil and control oil, fish and evening primrose oil, or both control oils. The control oils were corn oil and corn with wheat germ oil. All groups experienced a 10.6% to 15.5% decrease in days with pain. Neither fish oil nor evening primrose oil showed benefit over corn and wheat germ oils. Fish oil was associated with increased gastrointestinal adverse effects, whereas evening primrose oil had no more adverse effects than control oils. Proposed explanations for these findings include lack of effect of any oil, similar effect of all the oils or the vitamin E used with them to prevent oxidation, and the effect of time and care on improving pain.
Thus, results of studies and clinical series assessing evening primrose oil in the treatment of mastalgia are conflicting (Table 5). Evening primrose oil also has shown variable effectiveness for cyclic breast symptoms in studies of women with premenstrual syndrome.
Studies involved subjects with disturbing, persistent breast pain. Studies that primarily evaluated premenstrual syndrome were not included. EPO = evening primrose oil; FO = fish oil; LAS = linear analog scale (pain rating); NR = not reported.
EPO not different from placebo (gastric, skin, weight gain). FO and FO + EPO adverse effects increased from placebo (gastric)
Randomized, double-blind trial with factorial design (N=120) and 4 groups: (1) FO + control, (2) EPO + control, (3) FO + EPO, (4) both controls. All groups showed decrease in pain severity and % days with pain; neither EPO nor FO had benefit over control oils (P=.73)
* Studies involved subjects with disturbing, persistent breast pain. Studies that primarily evaluated premenstrual syndrome were not included. EPO = evening primrose oil; FO = fish oil; LAS = linear analog scale (pain rating); NR = not reported.
The proposed mechanism for evening primrose oil is based on the finding that women with cyclic breast pain have abnormal fatty acid profiles (increased saturated fatty acid esters, palmitic acid, and stearic acid) that may cause hypersensitivity of the breast epithelium to circulating hormones.
Evening primrose oil is available as a nutritional supplement to women worldwide. Typically 9% gamma-linolenic acid by weight, the dosage used for breast pain has been 3000 mg/d (in divided doses). Response to therapy is best assessed at 6 months because patients may continue to improve after 3 months of treatment.
Potential interaction with medications and other herbal medicinals also must be considered. Gamma-linolenic acid may affect the seizure threshold; for this reason, some researchers advise against its use in patients requiring anticonvulsant therapy.
The safety of evening primrose oil during pregnancy or lactation has not been established. Although widely considered effective, its benefits are only modestly better than placebo in some studies, and views differ regarding its therapeutic value for breast pain.
Soy.—Soy is a rich source of the isoflavones genistein and daidzen, which exert their effect by binding to estrogen receptors (preferentially the β-receptor subtype).
These hormonal changes provide a theoretical basis for the use of dietary soy or supplements for treatment of cyclic mastalgia. However, investigation into the effect of soy on breast epithelium has yielded mixed results. Some studies revealed markers of increased proliferation,
To date, no well-designed studies of soy to ameliorate symptoms of mastalgia are known.
Other Nutritional Supplements and Herbal Agents.— Interest is growing in herbal agents, nutritional supplements, and alternative strategies for treatment of breast pain.
A few of these have undergone preliminary study with regard to their effectiveness. In an open, uncontrolled study of the fruit extract of Vitex agnus-castus (chaste tree berry) in 1634 subjects for 3 menstrual cycles, 93% of the subjects reported improvement in symptoms related to premenstrual syndrome. In subjects in whom breast pain was the predominant symptom, the pain was less severe after treatment. Few adverse effects were identified, and 81% of subjects rated their status after treatment as much better or very much better.
In light of the frequency of breast pain, additional research must clarify the therapeutic value of improved mechanical support, relaxation techniques, dietary adjustments, nutritional supplements, herbal medicinals, and other nonpharmacological interventions.
Simple Analgesics
Surprisingly, there has been little investigation into simple analgesics, such as acetaminophen and nonsteroidal anti-inflammatory agents, for breast pain. In one uncontrolled study of 60 women with mastalgia treated with the oral nonsteroidal anti-inflammatory agent nimesulide (100 mg twice daily), breast pain decreased or resolved after 15 days.
Topical application of the nonsteroidal anti-inflammatory agents diclofenac and piroxicam yielded satisfactory relief in 21 (81%) of 26 women with severe cyclic, noncyclic, and surgical scar-related breast pain.
Recently, a randomized blinded study of a topical nonsteroidal anti-inflammatory agent showed significant pain reduction in 60 subjects with cyclic mastalgia and 48 subjects with noncyclic mastalgia compared with placebo. No adverse effects occurred.
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