Continuing Education Activity

Mastodynia or breast pain, also called mastalgia can occur both in women and men, but it presents more commonly in women. While most patients do not require treatment, the importance of determining an etiology for breast pain is pivotal. Breast pain is uncommonly found in patients with breast cancer. This activity focuses on the role of the interprofessional team in the evaluation, treatment, and management of breast pain.

Objectives:

• Identify the etiology of mastodynia.
• Outline the evaluation of mastodynia.
• Review management options available for mastodynia.
• Explain the importance of improving care coordination among the interprofessional team to improve outcomes for patients with mastodynia.

Introduction

Mastodynia is the medical term describing the common symptom of breast pain, also labeled as mastalgia. This symptom can occur in both men and women, but it presents more often in women, with the severity of the pain varying from mild and self-limited to severe pain. Mastodynia is usually related to a benign etiology and affects up to two-thirds of all women in their reproductive age.[1]

Although a small number of patients, around 15%, require pain-relieving therapy, it is of high importance to conduct a proper evaluation. A complete exam can involve a clinical breast exam, imaging, and a detailed, comprehensive history to determine the etiology of the pain. Some common causes of mastodynia include psychological disorders, hormonal variations such as premenstrual syndrome, or breast cancer.[2]

The primary concern of patients with breast pain, which leads them to seek medical attention, is the worry of being diagnosed with breast cancer. However, this is a relatively rare etiology of breast pain. Patients typically respond well to medical reassurance and stop pursuing medical evaluation once cancer has been ruled out.

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]

• 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]

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.

• 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]

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]

Deterrence and Patient Education

Breast pain is a common symptom among women, with up to 70% of women having an episode in their life that will make them consider seeking medical attention. However, only 36% of women will consult a physician about their breast pain. The main reason they will seek medical care is the fear of potentially having breast cancer. An alternative reason for patients seeking medical attention is because of the interference of mastodynia with their activities of daily living.

It is of importance to advise patients to be up to date with breast cancer screening and in case of breast pain episodes, to seek medical attention with their primary physician or OB/GYN. The reason it is recommended patients seek medical attention is to undergo a thorough history and physical examination and potentially breast imaging based on pain etiology and age.

Breast pain can be classified as cyclical, noncyclical, or extramammary. The importance of reaching the proper classification of breast pain is to aid accurate diagnosis and treatment to help reduce pain episodes and improve quality of life while minimizing adverse effects.

The first treatment consideration should be conservative such as physical support, acetaminophen, and NSAIDs. Patients should be advised that if they are not experiencing relief after six months, their physician may consider second-line therapy. During this process, physicians should include patients in the decision-making process and educate them about the diverse side effects expected. Patients should also be warned of signs to watch out for that could indicate a dangerous underlying diagnosis.

Enhancing Healthcare Team Outcomes

Mastodynia is a common symptom among women that can vary from mild to self-limited pain. Women often require minimal treatment given the relapsing and remitting course of symptoms. The prognosis depends on the patient's age and the category of mastalgia. To make the correct diagnosis, the provider must perform a thorough physical exam and appropriate imaging studies.

It is the provider's responsibility to make their judgment regarding the suitable treatment for a particular individual. It is important to consult with an interprofessional team of specialists in making the diagnosis. This team can include: nurses to assist with patient education and testing, radiologists for their vital role in determining the cause of breast pain using various breast imaging modalities, nutritionists to create a dietary regimen low in processed fat and high in fiber which has been shown to improve mastalgia by lowering estrogen levels.[42] [Level 2] Additional involvement can be beneficial from endocrinologists for the initiation of hormonal replacement therapies such as danazol, which has been shown to improve symptoms of mastalgia in 80% of women and some cases, even specialists in holistic medicine (acupuncturists and kinesiologists) can be beneficial. [Level 1] Another approach can involve psychotherapy, where evidence from a cohort study has demonstrated that 70% of mastalgia could be managed effectively by providing reassurance alone, with no need for pharmacological intervention.[43][44] [Level 3]

To improve patient outcomes, it is important to take into consideration an evidence-based approach to mastodynia treatment along with strong communication with the patient and other physicians.

Review Questions

• Access free multiple choice questions on this topic.
• Comment on this article.

References

1.

Olawaiye A, Withiam-Leitch M, Danakas G, Kahn K. Mastalgia: a review of management. J Reprod Med. 2005 Dec;50(12):933-9. [PubMed: 16444894]

2.

Padden DL. Mastalgia: evaluation and management. Nurse Pract Forum. 2000 Dec;11(4):213-8. [PubMed: 11220018]

3.

Rungruang B, Kelley JL. Benign breast diseases: epidemiology, evaluation, and management. Clin Obstet Gynecol. 2011 Mar;54(1):110-24. [PubMed: 21278510]

4.

Stachs A, Stubert J, Reimer T, Hartmann S. Benign Breast Disease in Women. Dtsch Arztebl Int. 2019 Aug 09;116(33-34):565-574. [PMC free article: PMC6794703] [PubMed: 31554551]

5.

Kataria K, Dhar A, Srivastava A, Kumar S, Goyal A. A systematic review of current understanding and management of mastalgia. Indian J Surg. 2014 Jun;76(3):217-22. [PMC free article: PMC4141056] [PubMed: 25177120]

6.

Scurr J, Hedger W, Morris P, Brown N. The prevalence, severity, and impact of breast pain in the general population. Breast J. 2014 Sep-Oct;20(5):508-13. [PubMed: 25041468]

7.

Ader DN, South-Paul J, Adera T, Deuster PA. Cyclical mastalgia: prevalence and associated health and behavioral factors. J Psychosom Obstet Gynaecol. 2001 Jun;22(2):71-6. [PubMed: 11446156]

8.

Jaafarnejad F, Adibmoghaddam E, Emami SA, Saki A. Compare the effect of flaxseed, evening primrose oil and Vitamin E on duration of periodic breast pain. J Educ Health Promot. 2017;6:85. [PMC free article: PMC5651668] [PubMed: 29114553]

9.

Goyal A. Breast pain. BMJ Clin Evid. 2011 Jan 17;2011 [PMC free article: PMC3275318] [PubMed: 21477394]

10.

Wisbey JR, Kumar S, Mansel RE, Peece PE, Pye JK, Hughes LE. Natural history of breast pain. Lancet. 1983 Sep 17;2(8351):672-4. [PubMed: 6136808]

11.

Smith RL, Pruthi S, Fitzpatrick LA. Evaluation and management of breast pain. Mayo Clin Proc. 2004 Mar;79(3):353-72. [PubMed: 15008609]

12.

Maddox PR, Mansel RE. Management of breast pain and nodularity. World J Surg. 1989 Nov-Dec;13(6):699-705. [PubMed: 2696222]

13.

Peters F, Diemer P, Mecks O, Behnken L LJ. Severity of mastalgia in relation to milk duct dilatation. Obstet Gynecol. 2003 Jan;101(1):54-60. [PubMed: 12517645]

14.

Hafiz SP, Barnes NLP, Kirwan CC. Clinical management of idiopathic mastalgia: a systematic review. J Prim Health Care. 2018 Dec;10(4):312-323. [PubMed: 31039960]

15.

Minton JP, Foecking MK, Webster DJ, Matthews RH. Response of fibrocystic disease to caffeine withdrawal and correlation of cyclic nucleotides with breast disease. Am J Obstet Gynecol. 1979 Sep 01;135(1):157-8. [PubMed: 224703]

16.

Wang K, Yee C, Tam S, Drost L, Chan S, Zaki P, Rico V, Ariello K, Dasios M, Lam H, DeAngelis C, Chow E. Prevalence of pain in patients with breast cancer post-treatment: A systematic review. Breast. 2018 Dec;42:113-127. [PubMed: 30243159]

17.

Iddon J, Dixon JM. Mastalgia. BMJ. 2013 Dec 13;347:f3288. [PubMed: 24336097]

18.

Brown N, Burnett E, Scurr J. Is Breast Pain Greater in Active Females Compared to the General Population in the UK? Breast J. 2016 Mar-Apr;22(2):194-201. [PubMed: 26661830]

19.

Goodwin PJ, Miller A, Del Giudice ME, Singer W, Connelly P, Ritchie JW. Elevated high-density lipoprotein cholesterol and dietary fat intake in women with cyclic mastopathy. Am J Obstet Gynecol. 1998 Aug;179(2):430-7. [PubMed: 9731849]

20.

Brisbine BR, Steele JR, Phillips EJ, McGhee DE. Breast pain affects the performance of elite female athletes. J Sports Sci. 2020 Mar;38(5):528-533. [PubMed: 31918624]

21.

Ngô C, Seror J, Chabbert-Buffet N. [Breast pain: Recommendations]. J Gynecol Obstet Biol Reprod (Paris). 2015 Dec;44(10):938-46. [PubMed: 26541567]

22.

Dzoic Dominkovic M, Ivanac G, Bojanic K, Kralik K, Smolic M, Divjak E, Smolic R, Brkljacic B. Exploring Association of Breast Pain, Pregnancy, and Body Mass Index with Breast Tissue Elasticity in Healthy Women: Glandular and Fat Differences. Diagnostics (Basel). 2020 Jun 10;10(6) [PMC free article: PMC7345881] [PubMed: 32532143]

23.

Harvey JA, Mahoney MC, Newell MS, Bailey L, Barke LD, D'Orsi C, Hayes MK, Jokich PM, Lee SJ, Lehman CD, Mainiero MB, Mankoff DA, Patel SB, Reynolds HE, Sutherland ML, Haffty BG. ACR Appropriateness Criteria Palpable Breast Masses. J Am Coll Radiol. 2016 Nov;13(11S):e31-e42. [PubMed: 27814822]

24.

Expert Panel on Breast Imaging: Jokich PM, Bailey L, D'Orsi C, Green ED, Holbrook AI, Lee SJ, Lourenco AP, Mainiero MB, Moy L, Sepulveda KA, Slanetz PJ, Trikha S, Yepes MM, Newell MS. ACR Appropriateness Criteria^® Breast Pain. J Am Coll Radiol. 2017 May;14(5S):S25-S33. [PubMed: 28473081]

25.

Harper AP, Kelly-Fry E, Noe JS. Ultrasound breast imaging-the method of choice for examining the young patient. Ultrasound Med Biol. 1981;7(3):231-7. [PubMed: 7268931]

26.

Holbrook AI. Breast Pain, A Common Grievance: Guidance to Radiologists. AJR Am J Roentgenol. 2020 Feb;214(2):259-264. [PubMed: 31799872]

27.

Howard MB, Battaglia T, Prout M, Freund K. The effect of imaging on the clinical management of breast pain. J Gen Intern Med. 2012 Jul;27(7):817-24. [PMC free article: PMC3378742] [PubMed: 22331398]

28.

Holland PA, Gateley CA. Drug therapy of mastalgia. What are the options? Drugs. 1994 Nov;48(5):709-16. [PubMed: 7530628]

29.

Duijm LE, Guit GL, Hendriks JH, Zaat JO, Mali WP. Value of breast imaging in women with painful breasts: observational follow up study. BMJ. 1998 Nov 28;317(7171):1492-5. [PMC free article: PMC28731] [PubMed: 9831579]

30.

Preece PE, Mansel RE, Bolton PM, Hughes LM, Baum M, Gravelle IH. Clinical syndromes of mastalgia. Lancet. 1976 Sep 25;2(7987):670-3. [PubMed: 60528]

31.

Hadi MS. Sports Brassiere: Is It a Solution for Mastalgia? Breast J. 2000 Nov;6(6):407-409. [PubMed: 11348400]

32.

Goyal A, Mansel RE., Efamast Study Group. A randomized multicenter study of gamolenic acid (Efamast) with and without antioxidant vitamins and minerals in the management of mastalgia. Breast J. 2005 Jan-Feb;11(1):41-7. [PubMed: 15647077]

33.

Russell LC. Caffeine restriction as initial treatment for breast pain. Nurse Pract. 1989 Feb;14(2):36-7, 40. [PubMed: 2927749]

34.

Colak T, Ipek T, Kanik A, Ogetman Z, Aydin S. Efficacy of topical nonsteroidal antiinflammatory drugs in mastalgia treatment. J Am Coll Surg. 2003 Apr;196(4):525-30. [PubMed: 12691925]

35.

Fentiman IS, Powles TJ. Tamoxifen and benign breast problems. Lancet. 1987 Nov 07;2(8567):1070-2. [PubMed: 2889976]

36.

Srivastava A, Mansel RE, Arvind N, Prasad K, Dhar A, Chabra A. Evidence-based management of Mastalgia: a meta-analysis of randomised trials. Breast. 2007 Oct;16(5):503-12. [PubMed: 17509880]

37.

Sutton GL, O'Malley VP. Treatment of cyclical mastalgia with low dose short term danazol. Br J Clin Pract. 1986 Feb;40(2):68-70. [PubMed: 3707831]

38.

Dixon JM. Hormone replacement therapy and the breast. BMJ. 2001 Dec 15;323(7326):1381-2. [PMC free article: PMC1121850] [PubMed: 11744551]

39.

Talimi-Schnabel J, Fink D. [Not Available]. Praxis (Bern 1994). 2017;106(20):1101-1106. [PubMed: 28976254]

40.

Cunha MS, De Sousa X, Simões J. Bilateral Mastodynia: An Unusual Presentation of Calciphylaxis. Acta Med Port. 2019 Feb 01;32(1):86. [PubMed: 30753809]

41.

Groen JW, Grosfeld S, Wilschut JA, Bramer WM, Ernst MF, Mullender MM. Cyclic and non-cyclic breast-pain: A systematic review on pain reduction, side effects, and quality of life for various treatments. Eur J Obstet Gynecol Reprod Biol. 2017 Dec;219:74-93. [PubMed: 29059585]

42.

Boyd NF, McGuire V, Shannon P, Cousins M, Kriukov V, Mahoney L, Fish E, Lickley L, Lockwood G, Tritchler D. Effect of a low-fat high-carbohydrate diet on symptoms of cyclical mastopathy. Lancet. 1988 Jul 16;2(8603):128-32. [PubMed: 2899188]

43.

Barros AC, Mottola J, Ruiz CA, Borges MN, Pinotti JA. Reassurance in the Treatment of Mastalgia. Breast J. 1999 May;5(3):162-165. [PubMed: 11348279]

44.

O'Brien PM, Abukhalil IE. Randomized controlled trial of the management of premenstrual syndrome and premenstrual mastalgia using luteal phase-only danazol. Am J Obstet Gynecol. 1999 Jan;180(1 Pt 1):18-23. [PubMed: 9914571]

Disclosure: Saul Grullon declares no relevant financial relationships with ineligible companies.

Disclosure: Samuel Bechmann declares no relevant financial relationships with ineligible companies.