CAFFEINE BREAST PAIN

AND

REVISITING THE CONNECTION

CARRIE CHASE, RN, MS, NP-C JAN WELLS, RN, MS, NP-C SUSAN ELEY, PhD, FNP-BC

For decades, women have been counseled by their health care providers to avoid caffeine and other sources of methylxanthines (e.g., coffee, chocolate, tea and theophylline) to manage cyclical breast pain. Yet such instructions conict with available scientic evidence.

It was previously postulated that methylxanthines cause a uctuation in hormone levels, which, in turn, contributed to breast pain. Even today, a quick Internet search of ca eine and breast pain nds legitimate health care providers suggesting ca eine avoidance as therapeutically valid for breast pain relief (California Paci c Medical Center, 2010). Some recently published clinical textbooks also recommend that patients refrain from ca eine consumption (Ferri, 2010).

Reviewing the Literature

To examine the evidence surrounding this issue, we conducted a literature review utilizing MEDLINE, PubMed, ScienceDirect, Oxford Journals and CINAHL to identify studies (limited to English-language studies) of the topic. Terms searched included breast pain, mastalgia, methylxanthines, ca eine, breast nodularity and breast lumps.

Bottom Line
For decades, women with mastalgia have been advised to avoid caffeine, despite a lack of clear evidence. Several studies have failed to nd a denitive connection between caffeine and mastalgia. Nurses can help provide the most current evidence-based information to women seeking treatment for mastalgia.

experience increased pain with physical and sexual activity. Some describe the breast pain as being dull, heavy or aching (Smith, Pruthi, & Fitzpatrick, 2004). For most women with cyclical pain, discomfort increases until menstruation begins, at which time it fades until the next luteal cycle. Researchers studying this phasic process theorize that hormones play a particular role, but speci c hormones have not been consistently identi ed. However, increased thyrotropin-induced prolactin secretion has been noted in patients with mastalgia (Smith et al., 2004). Although the pain is usually bilateral, it may be more intense in one breast than the other. e pain may also radiate into the axillary region and arm. Its estimated that about 40 percent of women experience cyclic mastalgia during their premenopausal years (Rosolowich et al., 2006). However, this number may be underestimated, as evidenced by one 10-year study of 1,171 women attending an ob/gyn clinic in the United States, in which 69 percent reported breast pain or discomfort before the start of their menstrual cycle (Smith et al.). Resolution of cyclic pain usually occurs during pregnancy or at the time of menopause, where it is natural or surgical.

Noncyclical Breast Pain

As its name suggests, noncyclical pain does not vary with menses and is less common than cyclic pain. Noncyclical pain is usually unilateral and more localized than cyclical pain, and has been described as burning, achy and sore. Its generally experienced by older women, usually in their 40s or 50s, with many postmenopause. Noncyclical pain can be related to breast trauma, mastitis or benign tumors, but o en a cause is never identi ed (Townsend, Beachaump, Evers, & Mattox, 2007). In ammatory breast cancer, although rare, may also cause noncyclical pain. Symptoms may include redness, swelling, warmth, a feeling of heaviness, tenderness, burning, aching and breast enlargement. e symptoms usually develop rapidly over weeks and/or months and may include skin changes (Merajver & Sabel, 2004).

About Mastalgia
Cyclical Breast Pain
ere are three main categories of mastalgia: cyclical, noncyclical and extra-mammary. Cyclical breast pain is typically related to menses and begins during the luteal phase of the menstrual cycle, when ovulation occurs and the estrogen to progesterone ratio is highest (Rosolowich, Saettler, & Szuck, 2006). Its the most common type of breast pain and accounts for more than two-thirds of o ce visits for mastalgia evaluation. While minor discomfort a few days before the onset of menses is considered normal, cyclic breast pain is usually more intense and occurs more than 7 days per month. Women who have cyclic pain may miss work and school, have interruption of sleep and
Carrie Chase, RN, MS, NP-C, is a certi ed registered nurse practitioner working in rheumatology and pain management at Mid-Maryland Musculoskeletal Institute in Frederick, MD. Jan Wells, RN, MS, NP-C, is a nurse practitioner working in neurology and pain management at Skaggs Medical Center in Branson, MO. Susan Eley, PhD, FNP-BC, is DNP program director and assistant professor at Indiana State University in Terre Haute, IN. e authors report no con icts of interest or relevant nancial relationships. Address correspondence to: humnbird1@earthlink.net.
DOI: 10.1111/j.1751-486X.2011.01649.x

Extra-Mammary Breast Pain

e third type of breast pain is extra-mammary pain, which refers to pain originating in areas other than the breast. It includes musculoskeletal pain, cardiac pain, gastrointestinal pain and Tietze syndrome, a form of costochondritis of the upper front of the chest (Smith et al., 2004). Pain can also occur with shingles, where it is usually found unilaterally and is accompanied by the characteristic zoster rash. Medications such as digoxin, spironolactone and chlorpromazine may also contribute to extra-mammary breast pain (Alvi, 2007).

Breast Pain and Fibrocystic Changes

Cyclical breast pain is commonly associated with brocystic changes, which used to be called brocystic breast disease.

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ITS ESTIMATED THAT ABOUT 40 PERCENT OF WOMEN EXPERIENCE CYCLIC MASTALGIA DURING THEIR PREMENOPAUSAL YEARS
While brocystic changes are o en described as a clinical nding, microscopic evaluation is necessary for accurate diagnosis. Microscopic tissue samples of brocystic breast tissue reveal brosis and cysts in varying sizes and numbers (Miltenburg & Speights, 2008). Other histologic ndings of brocystic breast tissue include apocrine metaplasia, adenosis and papillomatosis. Two ndings associated with increased risk of breast cancer are ductal epithelial hyperplasia with atypia, and apocrine metaplasia with atypia. Otherwise, women with brocystic changes are at no increased risk of developing carcinoma than women without such breast characteristics (Katz, Lentz, Lobo, & Gershenson, 2007). Women with bothersome brocystic changes report dull or aching pain, which tends to peak in their 30s and 40s. Upon palpation, breasts may feel lumpy or nodular, somewhat solid, and patients may report tenderness (although tenderness is common for most patients undergoing breast examination). Patients may report that their breasts change in size and density as their menstrual cycles progress. most researchers have studied the relationship of ca eine and its related substances on the physical breast changes that presumably cause pain in the patient. Xanthine is a purine, or nitrogenous base substance, found frequently in nature. Methylxanthines are xanthine derivatives found in products such as cocoa, black teas and foods like chocolate. Ca eine, theophylline and aminophylline are methylxanthines. Methylxanthines produce bronchial smooth muscle relaxation, stimulate diuresis and act as mild cardiac and central nervous system stimulants ( omas & Venes, 1997). In 1979, Minton, Foecking, Webster, and Matthews published research ndings indicating discovery of an association between consumption of ca eine and breast pain. ey found that biopsied breast specimens in women with reported breast pain contained greater numbers of cyclic nucleotides, such as adenosine monophosphate (c-AMP) and guanosine monophosphate (c-GMP). e presence of these nucleotides leads to a stimulation of protein kinases and, theoretically, increased production of brous tissue and cystic uid. A subsequent dietary review indicating a greater ca eine intake in women with greater levels of c-AMP and c-GMP inspired Mintons group to develop the hypothesis that a reduction in ca eine consumption would cause a subsequent reduction in

Background on the Caffeine Connection

Because nodularity and histologic changes are objectively measurable and pain is subjective and unique to the individual,

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breast pain complaints. According to their research, 75 percent of study participants reported a reduction in breast pain when their ca eine intake was stopped (Minton et al.).

Subsequent Studies
e subjective nature of portions of Mintons research inspired others to initiate study on the topic, and most results were either inconclusive or were unable to replicate Mintons results. Over the decade following the 1979 study by Minton et al., two randomized controlled trials on the connection between breast symptom and ca eine consumption were undertaken. e rst trial consisted of 158 women with breast concerns (Ernster, Mason, & Goodson, 1982). Women were assigned to one of two groups; the rst group abstained from drinks or foods containing methylxanthines, and the other group followed no dietary restrictions. Each patient was examined at the beginning and end of the 4-month study. Results found measurable but minute change in the methylxanthine-abstaining group. Preand poststudy mammograms provided negligible support for the methylxanthine hypothesis (Ernster et al.).

histological samples and found no evidence of correlation between benign breast changes and methylxanthines. A controlled clinical trial in Italy examined 192 women whose brocystic changes had been documented clinically and thermographically. e population was divided into four groups. Participants in the rst group abstained from methylxanthines, the second group abstained from alcohol, the third group abstained from both substances and the fourth group had no dietary advice given. At the end of 6 months, 84 percent of the population was still intact, and no signi cant di erences in signs and symptoms were detected between the groups (Parazzini, La Vecchia, Riundi, Pampallona, & Scanni, 1986).

Recent Literature
Since it was previously hypothesized that benign breast disease (including brocystic changes) was suspected of causing increased risk for breast cancer, other dietary intake studies were conducted to determine any such relationships. Webb et al. (2004) used the Nurses Health Study II to examine the

THE STUDY FOUND THAT REDUCING CAFFEINE CONSUMPTION FAILED TO RESULT IN ANY SIGNIFICANT LESSENING IN PALPABLE BREAST LUMPS, PAIN OR TENDERNESS
e second study was a single-blind, randomized trial that examined 56 subjects with benign proliferative breast disease. Participants were randomly assigned to one of three groups: (1) control group with no dietary restrictions, (2) placebo group following a cholesterol-free diet and (3) experimental group abstaining from ca eine. Subjects were examined and interviewed at the beginning and at 2- and 4-month intervals. e study found that reducing ca eine consumption failed to result in any signi cant lessening in palpable breast lumps, pain or tenderness (Allen & Froberg, 1987). Other case-controlled studies were performed during the same period of time. One directly implicated recent interest in the methylxanthine/benign breast disease connection as impetus for research. Its comparison of 323 women with benign breast disease with 1,458 control subjects who had no di erences in co ee or tea consumption revealed no symptomatic di erence between the groups. e authors concluded there was a lack of evidence to suggest that co ee or tea intake was related to resolution or reduction of breast symptoms (Marshall, Graham, & Swanson, 1982). A few years later, Schairer, Brinton, and Hoover (1986) released the results of their casecontrol study of 1,569 cases and 1,846 controls that indicated no correlation between cyclic breast pain and methylxanthine consumption. Additionally, they reported upon examination of e ect of dietary ca eine, ber and antioxidants on the incidence of benign breast disease and atypical hyperplasia. ey theorized that a dietary or environmental component must exist based on the higher incidence of breast cancer in the Western world when compared with Asia (Webb et al.). ey studied 328 women with biopsy-con rmed benign breast lesions. Four pathologists classi ed the benign tissues into three categoriesnormal (nonproliferative), proliferative without atypia and proliferative with atypia. Dietary factors studied included ca eine, fats, ber, vitamins A, C, E, folate and beta-carotene. Within the study population, it was noted that high ca eine intake was associated with current smoking, and smokers also had a lower rate of vitamin intake. Study results showed no relationship between reported or biopsycon rmed benign breast disease and intake of ca eine, animal fats or the studied vitamins. e authors noted the association of atypical hyperplasia was less for those taking vitamin supplements and increased in those with the highest quartile of ca eine ingestion; however, their comments were guarded based on the small sample size of 32 patients with biopsied atypia (Webb et al.). In 2009, Tang, Zhou, Wang, and Yu published a meta-analysis of nine case-control and nine cohort studies examining the relationship between breast cancer and co ee consumption.

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BOX 1

LEVELS OF EVIDENCE
I At least one randomized controlled trial II-1 Evidenced by controlled trials without randomization II-2 Evidenced by well-designed cohort or case-control studies II-3 Evidenced from comparisons between times or places with or without intervention III Information from respected authorities or expert panel

Current Guidelines, Publications and Recommendations

Society of Obstetricians and Gynaecologists of Canada
In 2006, the Society of Obstetricians and Gynaecologists of Canada (SOGC) published speci c guidelines for mastalgia management (Rosolowich et al., 2006). A thorough search of additional medical and professional organizations found no additional formal guidelines for comparison. e SOGC guidelines recommend strategies for e ective control of breast pain ranked on quality of evidence (see Box 1). Recommendations labeled as having Level I evidence are concluded from data obtained from at least one properly randomized controlled trial and are listed in Box 2. Level II evidence recommendations are based on properly designed controlled trials without randomization, well-designed cohort or case-controlled studies, or dramatic results from uncontrolled experiments (see Box 3). Level III recommendations are derived from committee reports, esteemed authorities, descriptive studies or clinical experience (see Box 4).

A borderline signi cant association of decreased risk of breast cancer with co ee consumption was noted in the United States and Europe but not in Asia, with increased risk that was only relevant if atypical hyperplasia was also present (Tang et al.). Tang et al. hypothesized that co ee consumption could decrease breast cancer risk, because studies in rats determined that ca eine reduces the size of benign mammary gland tumors and decreased the number of rats developing cancers. Co ee contains lignansantioxidants that are the precursor of enterolactone, a phytoestrogen. When present in greater concentrations, enterolactone has a theoretical relationship to lowered breast cancer risk. One study included in the meta-analysis reported that co ee consumption of greater than six cups per day was signi cantly related to a reduced risk of breast cancer in women with the BRCA-1 mutation (Tang et al.).

University of Michigan Health System

e University of Michigan Health System published a clinical guideline in 2007 for breast problems that addressed breast pain, including evaluation, diagnosis and recommendations. e guideline advises that breast pain without physical ndings should be screened for speci c medical conditions and medication usage. Four levels of evidence were referenced for the guideline, beginning with Grade A (randomized controlled trials), then extending to Grade B (controlled trials, no randomization), Grade C (observational trials) and nally to Grade D (opinion of expert panel; University of Michigan Health System, 2007). Recommendations include mammogram for breast pain in women over age 40, and a well- tting bra (Grade C recommendation),

BOX 2

LEVEL I EVIDENCE MASTALGIA RECOMMENDATIONS FROM THE SOCIETY OF OBSTETRICIANS AND GYNAECOLOGISTS OF CANADA
Women should not be advised to decrease caffeine intake to reduce breast pain. Vitamin E should not be considered for breast pain relief. Dietary axseed should be considered as a rst-line therapy for cyclical breast pain. The topical nonsteroidal anti-inammatory gel diclofenac 2% in pluronic lecithin organogel (PLO) should be considered for women with localized breast pain. are ineffective.

Daily tamoxifen 10 mg or danazol 200 mg should be considered when rst-line treatments

Source: Rosolowich et al. (2006).

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BOX 3

LEVEL II EVIDENCE MASTALGIA RECOMMENDATIONS FROM THE SOCIETY OF OBSTETRICIANS AND GYNAECOLOGISTS OF CANADA Reassurance and patient education is an A properly tting, supportive
bra should be considered for both cyclical and noncyclical breast pain. primrose oil lacks sufcient evidence for recommendation in treatment of breast pain. essential part of breast pain management and should be the rst-line treatment.

the guidelines, clear strength of the recommendations from the literature is not available. A comprehensive exploration of breast pain location, pain level and relationship to menstrual cycle or physical activities is indicated as part of the evaluation. Nonpharmacologic recommendations by the ICSI include a reduction in saturated dietary fat and a reduction or elimination of ca eine for those patients with high intake. Interestingly, the guideline states that study-based evidence exists for the recommendation to reduce dietary fat, but that evidence for ca eine reduction is inconsistent and anecdotal (ICSI).

American Congress of Obstetricians and Gynecologists

e American Congress of Obstetricians and Gynecologists (ACOG) has not issued similar guidelines, but in September 2010 published a continuing medical education article on the topic of benign breast disease (Pearlman & Gri n, 2010). Options discussed for benign mastalgia include reassurance, the use of gamma-linolenic acid (the active ingredient of evening primrose oil) and use of oral and topical NSAIDs. e article states that there is no conclusive evidence of demonstrated e cacy for avoidance of ca eine or other methylxanthines or salt, or use of diuretics for improvement of breast pain symptoms (Pearlman & Gri n). ACOG has published limited patient education on mastalgia. Mention of breast pain is incorporated in its 2000 patient education pamphlet Fibrocystic Breast Changes, with avoidance of ca eine and salty foods suggested among the actions for breast pain relief (ACOG, 2000).

Use of evening

Source: Rosolowich et al. (2006).

Recommendations for Further Research

plus a 3- to 6-month trial of evening primrose oil, nonsteroidal anti-in ammatory drugs (NSAIDs) or topical diclofenac gel (Grade A recommendation) for women with a negative radiographic result. If no improvement occurs within a few months, the patient is referred to a breast specialist (Grade C recommendation). If physical ndings are present at the initial exam or the patient has an abnormal mammogram, then referral is made immediately (University of Michigan Health System). Reduction of ca eine intake is not mentioned as a recommendation in this guideline as a breast pain remedy (Box 5). Some natural substances and dietary practices show promise for e cacy in managing mastalgia, but they need further study. A Canadian double-blind, placebo-controlled study indicated

BOX 4

LEVEL III EVIDENCE MASTALGIA RECOMMENDATIONS FROM THE SOCIETY OF OBSTETRICIANS AND GYNAECOLOGISTS OF CANADA Changes in dose, formulation, scheduling or
discontinuation of hormone therapy should be considered for women with mastalgia who use those products.

Institute for Clinical Systems Improvement

e Institute for Clinical Systems Improvement (ICSI) issued a new breast disease guideline in 2010 (ICSI, 2010). e guidelines stress the importance of history-taking and physical examination for other breast pain sources, including the spinal column, upper extremity and thorax. Evidence grading for ICSI recommendations were based on either primary reports of new data collection, or reports based on meta-analysis, synthesized collections or medical opinion (ICSI). From reviewing

Mastalgia should not be treated by use of mastectomy or partial mastectomy.

Source: Rosolowich et al. (2006).

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BOX 5

SUMMARY OF LEVELS OF EVIDENCE REGARDING MASTALGIA GUIDELINES

Guideline Caffeine reduction
SOGC University of Michigan Health System ICSI ACOG

I (lacks support)

May help; no supporting evidence A +

States no supporting evidence +

Evening primrose oil Flaxseed Hormone review and/or changes Hot/cold packs Mastectomy NSAIDS Reassure Supportive bra Tamoxifen or danazol Topical diclofenac Vitamin E Other KEY:

II (lacks support) I III III

+ + A + R + +

II II I I I (lacks support)

+ C

A A No evidence for diuretic use, sodium reduction

I, A: Randomized control trials II, B: Control trials without randomization; cohort, case-controlled III, C: Committee reports, authorities, descriptive studies D: Expert opinion or panel +: Stated, evidence strength not reported R: Consensus statement or report

notable improvement in a group of women with severe cyclical breast pain a er they incorporated 25 grams of dietary axseed into their daily diets. In another small, randomized controlled trial, 60 percent of a group of women with cyclical breast pain had reduced swelling, tenderness and nodularity when they followed a low-fat diet. Iso avones were found to reduce cyclical mastalgia in yet another small, double-blind randomized controlled trial. Chasteberry also was researched in a randomized controlled trial and was found to be e ective (Rosolowich et al., 2006).

Where Do We Go From Here?

Women o en seek advice about breast pain from their health care providers out of concerns about breast cancer. Most o en,

they are reassured that pain is rarely a symptom of cancer. For many patients, this is all the management they need, in addition to promotion of continued self-breast exam, careful history taking and yearly professional breast examination. However, for those with severe pain, mastalgia may interfere with quality of life. While some may opt for pharmacologic pain management, the potential side e ects of these drugs may be considerable. Others will opt for nonpharmacologic strategies or more natural options to reduce the pain. e 1979 publication of the study by Minton et al. was the apparent genesis of the avoid ca eine to reduce breast pain advice, and since then many thousands of women and their health care providers continue to believe and follow such

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A CANADIAN DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY INDICATED NOTABLE IMPROVEMENT IN A GROUP OF WOMEN WITH SEVERE CYCLICAL BREAST PAIN AFTER THEY INCORPORATED 25 GRAMS OF DIETARY FLAXSEED INTO THEIR DAILY DIETS
recommendations. Successful implementation of existing evidence-based recommendations for mastalgia management can be achieved when accurate, e ective information is shared with patients by health care providers. E ective patient education and provider-patient discussions about alternative strategies for pain relief allow for personalized tailoring of treatment. When patients are educated about the origins of breast pain and what is within the range of normal and abnormal, theyll be able to achieve greater knowledge about their bodies. Finally, there may be an improvement in quality of life for patients who are simply trying to enjoy their ca eine-containing substances without feeling guilty. NWH
Miltenburg, D. M., & Speights, V. O. Jr. (2008). Benign breast disease. Obstetrics and Gynecology Clinics of North America, 35, 285300. Minton, J., Foecking, M., Webster, D., & Matthews, R. (1979). Ca eine, cyclic nucleotides, and breast disease. Surgery, 86(1), 105109. Parazzini, F., La Vecchia, C., Riundi, R., Pampallona, S., & Scanni, A. (1986). Methylxanthine, alcohol-free diet and brocystic breast disease (a factorial clinical trial). Surgery, 99, 576580. Pearlman, M. & Gri n, J. (2010). Benign breast disease. Obstetrics and Gynecology, 16(3), 747758. Rosolowich, V., Saettler, E., & Szuck, B. (2006). Mastalgia. SOGC clinical guideline. Ottawa, Canada: Society of Obstetricians and Gynaecologists of Canada. Retrieved from http://www.sogc.org/ guidelines/public/170E-CPG-January2006.pdf Schairer, C., Brinton, L. A., & Hoover, R. N. (1986). Methylxanthines and benign breast disease. American Journal of Epidemiology, 124(4), 603611. Smith, R., Pruthi, S., & Fitzpatrick, L. (2004). Evaluation and management of breast pain. Mayo Clinic Proceedings, 29, 353373. Tang, N., Zhou, B., Wang, B., & Yu, R. (2009). Co ee consumption and risk of breast cancer: A metaanalysis. American Journal of Obstetrics and Gynecology, 200(3), 290.e1290.e9. omas, C., & Venes, D. (1997). Tabers cyclopedic medical dictionary. Philadelphia: F.A. Davis. Townsend, C., Beachaump, R., Evers B., & Mattox, K. (2007). Fibrocystic changes and breast pain. In C. Townsend, R. Beachaump, B. Evers, & K. Mattox (Eds.), Sabiston textbook of surgery (18th ed.). Philadelphia: Elsevier. University of Michigan Health System. (2007). Common breast problems: Guidelines for clinical care. Retrieved from http://cme. med.umich.edu/pdf/guideline/breast.pdf Webb, P. M., Byrne, C., Schnitt, S. J., Connolly, J. L., Jacobs, T. W., Baer, H. J., et al. (2004). A prospective study of diet and benign breast disease. Cancer Epidemiology, Biomarkers and Prevention, 13(7), 11061113.

References
Allen, S., & Froberg, D. (1987). e e ect of decreased ca eine consumption on benign proliferative breast disease: A randomized clinical trial. Surgery, 101(6), 720730. Alvi, M. R. (2007). Breast lumps and pain. In eMedicine. Retrieved from http://www.emedicinehealth.com/breast_lumps_and_pain/ article_em.htm American Congress of Obstetricians and Gynecologists. (2000). Fibrocystic breast changes. Retrieved from http://www.acog.org/ publications/patient_education/bp138.cfm?printerFriendly=yes California Paci c Medical Center. (2010). Breast pain. Retrieved from http://www.cpmc.org/services/women/breast/breast_ about.html Ernster, E., Mason, L., & Goodson, W. III. (1982). E ects of caffeine-free diet on benign breast disease: A randomized trial. Surgery, 91(3), 263267. Ferri, F. (2010). Mastodynia. Ferris Clinical Advisor 2011 (1st ed.). Philadelphia: Elsevier. Institute for Clinical Systems Improvement. (2010). Breast disease. Retrieved from http://www.icsi.org/breast_disease_diagnosis/ diagnosis_of_breast_disease_2.html Katz, V., Lentz, G., Lobo R., & Gershenson, D. (2007). Comprehensive gynecology (5th ed.). Philadelphia: Elsevier. Marshall, J., Graham, S., & Swanson, M. (1982). Ca eine consumption and benign breast disease: A case-control comparison. American Journal of Public Health, 72(6), 610612. Merajver, S. D., & Sabel, M. S. (2004). In ammatory breast cancer. In J. R. Harris, M. E. Lippman, M. Morrow, & C. K. Osborne (Eds.), Diseases of the breast (3rd ed.). Philadelphia: Lippincott, Williams and Wilkins.

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