Breast pain

Abstract

Introduction

Breast pain may be cyclical (worse before a period) or non-cyclical, originating from the breast or the chest wall, and occurs at some time in 70% of women. Cyclical breast pain resolves spontaneously in 20% to 30% of women, but tends to recur in 60% of women. Non-cyclical pain responds poorly to treatment but tends to resolve spontaneously in half of women.

Methods and outcomes

We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for breast pain? We searched: Medline, Embase, The Cochrane Library, and other important databases up to February 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

Results

We found 11 studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

Conclusions

In this systematic review we present information relating to the effectiveness and safety of the following interventions: bra wearing, combined oral contraceptive pill, danazol, gonadorelin analogues, progestogens, tamoxifen, and topical or oral non-steroidal anti-inflammatory drugs (NSAIDs).

Key Points

Breast pain (mastalgia) may be cyclical (worse before a period) or non-cyclical, originating from the breast or the chest wall, and occurs at some time in 70% of women.

• Cyclical breast pain resolves spontaneously in 20% to 30% of women, but tends to recur in up to 60% of women.

• Non-cyclical pain responds poorly to treatment but tends to resolve spontaneously in about half of women.

• An accurate diagnosis of true breast pain should be made and other non-breast pathology should be excluded. Other differential diagnoses include pain arising from the chest wall.

Overall, the trials we found were small and of limited quality. There is a need for large, good-quality trials in this area.

We found limited evidence that topical diclofenac may be effective at relieving symptoms of cyclical and non-cyclical breast pain but has been associated with adverse effects.

• There is consensus that topical non-steroidal anti-inflammatory drugs (NSAIDs) are effective in relieving breast pain and should be considered as a first-line treatment, as the benefits are thought to outweigh the risk of adverse effects.

We found insufficient evidence to assess the effects of oral NSAIDs on breast pain.

We don't know whether topical NSAIDs are more effective than oral NSAIDs at reducing breast pain.

Danazol, tamoxifen, and gonadorelin analogues (goserelin) may reduce breast pain, but all can cause adverse effects. These agents would usually only be prescribed by a specialist.

• Danazol can cause weight gain, deepening of the voice, menorrhagia, and muscle cramps, and has androgenic effects on the fetus.

• There is consensus to limit the use of tamoxifen to no more than 6 months at a time under expert supervision, and with appropriate non-hormonal contraception, because of the high incidence of adverse effects including teratogenicity and venous thromboembolism.

• Goserelin injection is associated with vaginal dryness, hot flushes, decreased libido, oily skin or hair, decreased breast size, and irritability. There is consensus that goserelin injections should be reserved for severe refractory mastalgia and that treatment should be limited to 6 months.

• Danazol may be less effective than tamoxifen at reducing breast pain and has a less favourable adverse-effects profile compared with tamoxifen (10 mg daily).

• Tamoxifen (10 mg daily) under expert supervision, or danazol, may be considered when first-line treatments are ineffective.

• Tamoxifen (20 mg daily) may increase the risk of venous thromboembolism.

There is consensus that progestogens do not have a role in treating mastalgia.

We don't know whether the combined oral contraceptive pill or wearing a bra reduce breast pain, as we found no RCTs.

About this condition

Definition

Breast pain can be differentiated into cyclical mastalgia (worse before a menstrual period) or non-cyclical mastalgia (unrelated to the menstrual cycle). Cyclical pain is often bilateral, usually most severe in the upper outer quadrants of the breast, and may be referred to the medial aspect of the upper arm. Non-cyclical pain may be caused by true breast pain or chest wall pain, located over the costal cartilages. Specific breast pathology and referred pain unrelated to the breasts are not included in this review.

Incidence/ Prevalence

Up to 70% of women develop breast pain in their lifetime. Of 1171 US women attending a gynaecology clinic for any reason, 69% suffered regular discomfort, which was judged as severe in 11% of women, and 36% had consulted a doctor about breast pain.

Aetiology/ Risk factors

Breast pain is most common in women aged 30 to 50 years.

Prognosis

Cyclical breast pain resolves spontaneously within 3 months of onset in 20% to 30% of women. The pain tends to relapse and remit, and up to 60% of women develop recurrent symptoms 2 years after treatment. Non-cyclical pain responds poorly to treatment but may resolve spontaneously in about 50% of women.

Aims of intervention

To reduce breast pain and improve quality of life, with minimal adverse effects.

Outcomes

Breast pain score based on the number of days of severe (score 2) or moderate (score 1) pain experienced in each menstrual cycle; visual analogue score of breast pain, heaviness, or breast tenderness; questionnaires; quality of life; adverse effects.

Methods

Clinical Evidence search and appraisal February 2014. The following databases were used to identify studies for this systematic review: Medline 1966 to February 2014, Embase 1980 to February 2014, and The Cochrane Database of Systematic Reviews 2014, issue 1 (1966 to date of issue). Additional searches were carried out in the Database of Abstracts of Reviews of Effects (DARE) and the Health Technology Assessment (HTA) database. We also searched for retractions of studies included in the review. An information specialist identified titles and abstracts in an initial search, which an evidence scanner then assessed against predefined criteria. An evidence analyst then assessed full texts for potentially relevant studies against predefined criteria. An expert contributor was consulted on studies selected for inclusion. An evidence analyst then extracted all data relevant to the review. Study design criteria for inclusion in this review were: published RCTs and systematic reviews of RCTs in the English language, at least single-blinded, and containing more than 20 individuals, of whom more than 80% were followed up. There was no minimum length of follow-up. We excluded all studies described as 'open', 'open label', or not blinded unless blinding was impossible. We included RCTs and systematic reviews of RCTs, where harms of an included intervention were assessed, applying the same study design criteria for inclusion as we did for benefits. In addition, we used a regular surveillance protocol to capture harms alerts from organisations such as the FDA and the MHRA, which are added to the reviews as required. To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).

Table.

GRADE Evaluation of interventions for Breast pain.

Important outcomes	Breast pain, Quality of life
Studies (Participants)	Outcome	Comparison	Type of evidence	Quality	Consistency	Directness	Effect size	GRADE	Comment
What are the effects of treatments for breast pain?
1 (60)	Breast pain	Topical NSAIDs versus placebo	4	–2	0	0	0	Low	Quality points deducted for sparse data and sub-group analysis
1 (100)	Breast pain	Topical NSAIDs versus oral NSAIDs	4	–2	0	0	0	Low	Quality points deducted for sparse data and incomplete reporting of results
1 (40)	Breast pain	Oral NSAIDs versus placebo	4	–3	0	0	0	Very low	Quality points deducted for sparse data, no significance assessment of between-group difference, and unclear method of randomisation
1 (61)	Breast pain	Danazol versus placebo	4	–1	0	–1	0	Low	Quality point deducted for sparse data; directness point deducted for restricted population
1 (147)	Breast pain	Gonadorelin analogues (goserelin; luteinising hormone-releasing hormone analogues) versus placebo	4	–1	0	0	0	Moderate	Quality point deducted for sparse data
3 (241)	Breast pain	Tamoxifen versus placebo	4	–1	0	–1	0	Low	Quality point deducted for incomplete reporting of results; directness point deducted for uncertainty about definition of outcomes
2 (361)	Breast pain	Different doses of tamoxifen versus each other	4	–1	0	0	0	Moderate	Quality point deducted for incomplete reporting of results
2 (58)	Breast pain	Progestogens versus placebo	4	–3	0	0	0	Very low	Quality points deducted for sparse data, poor follow-up, and incomplete reporting of results
1 (64)	Breast pain	Danazol versus tamoxifen	4	–1	0	–1	0	Low	Quality point deducted for sparse data; directness point deducted for restricted population

We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size. Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasi-randomisation, sparse data [<200 people in the analysis]). Consistency: based on similarity of results across studies. Directness: based on generalisability of population or outcomes. Effect size: based on magnitude of effect as measured by statistics such as relative risk, odds ratio, or hazard ratio.

Glossary

Low-quality evidence

Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

Moderate-quality evidence

Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.

Very low-quality evidence

Any estimate of effect is very uncertain.

Premenstrual syndrome

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