Due to the increasing awareness of breast cancer, most women now seek advice from their general practitioner about breast pain symptoms. Female patients may present with a variety of symptoms that can range from relatively minor symptoms to severe symptoms significantly affecting quality of life. Heaviness and associated discomfort during the week prior to each menstrual cycle may be associated with tender, lumpy breast areas. Classically, in cyclical mastalgia, these symptoms will regress following the commencement of a period. Due to the fact that mastalgia is a common condition and occurs predominately within the reproductive years, it is best considered an alteration of the normal cyclical pattern. Therefore, a combination of reassurance and medical therapy will most often achieve a satisfactory clinical response in the majority of patients.

Symptoms
A detailed history listing potential risk factors for the development of breast pain (i.e., the use of the oral contraceptive pill (OCP) or HRT, pregnancies, menstrual history, diet and medication) is useful. It is important to define whether mastalgia is cyclical or noncyclical and also from exactly where the pain originates (i.e., from breast tissue or from the underlying chest wall.) Examples of symptoms originating from the underlying chest wall are Tietze’s syndrome (costochondritis), herpes zoster and radiculopathy secondary to lower cervical spondylosis.

Signs
Clinical examination may be entirely normal apart from tenderness confined to one area of the breast. Generalized bilateral tenderness may be observed. Associated focal or generalized nodularity may be present.

Examination of both axillae is usually normal.

Investigations
In women over 35 years of age, mammography is performed and this may be normal. Women with discrete areas of focal nodularity will undergo ultrasound and if necessary FNAB/core biopsy of the area to confirm its benign nature. No specific histological appearance is associated with this symptom.

Management

Although there is no definitive scientific evidence for it, several features suggest mastalgia is secondary to an underlying hormonal abnormality. The ack of evidence may be due to the difficulty of collecting data in light of daily and circadian variations in plasma hormonal levels. Current recommendations for management of women with mastalgia are based on theories related to possible etiology. The sheet anchor of management of these patients s reassurance of the benign nature of their condition.

Reduction of Caffeine
Recommendations to reduce caffeine intake are based on the hypothesis that methylxanthines cause proliferation of cells in the breast by increasing cyclic adenosine monophosphate (cAMP).  Tissue obtained from patients with breast disease has demonstrated increased sensitivity to biochemical stimulation by methylxanthines. Although there is no hard evidence that abstention of methylxanthines is beneficial to women with mastalgia, clinicians continue to recommend this to patients on the basis that anecdotal evidence does exist for improvement of mastalgia on a caffeine-free diet.

Reduced Intake of Dietary Fat
The hypothesis that fat increases endogenous hormonal levels thereby causing breast pain by a direct stimulatory effect, led to the suggestion that at restriction might relieve symptoms of mastalgia. There is some evidence to suggest that a reduced intake of dietary fat may help cyclical breast tenderness and swelling.

Gamma-Linolenic Acid (GLA)
Studies demonstrate low plasma levels of GLA (an essential fatty acid) in women with mastalgia. It is believed that a higher ratio of saturated to unsaturated fatty acids may alter the sensitivity of breast hormone receptors (both estrogen and progesterone).  Based on this hypothesis, administration of GLA in a dose of 320 mg daily for a minimum period of 3 months is recommended. Response rates of up to 58% in cyclical mastalgia and 38% in noncyclical mastalgia were observed in a study conducted at the Cardiff mastalgic clinic. 

In our experience, GLA is effective and has few side effects and patient compliance is good. It is our next line of management in addition to reassurance and advice regarding reduction in intake of caffeine and dietary fat.

Vitamin B6 - Pyridoxine
Vitamin B6 is still prescribed in the United Kingdom, although there is no evidence that it causes significant improvement in women with mastalgia.

Diuretics
There is no evidence that diuretics benefit in the management of mastalgia.

It is therefore inappropriate to consider this as a form of treatment for this disorder.

Hormonal Treatment

Danazol
Danazol is a synthetic steroid that competitively inhibits estrogen and progesterone receptors in the breast as well as production of ovarian steroids.

Randomized, controlled trials have demonstrated that danazol is beneficial in cyclical mastalgia in relatively low doses of 200 mg causing a reduction in pain and nodularity scores.  Our current recommendation is to commence therapy with danazol at a dose of 100 mg twice daily for two cycles, maintaining a record of breast pain using a breast pain chart. If the patient fails to respond to this therapy, either the dose may be increased or an alternative drug regimen adopted. Side effects of danazol include weight gain, hirsutism, irregular periods and headaches.

Tamoxifen
Tamoxifen is an estrogen-receptor inhibitor and is widely used in breast cancer. It is therefore not surprising that it has proven itself beneficial in the treatment of mastalgia.  This drug does not have a product license in the United Kingdom for treatment of mastalgia. In severe cases of refractory mastalgia unresponsive to gamma linolenic acid and danazol, however, it is reasonable to consider this drug, having fully explained to the patient the side effects and in particular the risks it poses to the endometrium. It is sensible to restrict usage of tamoxifen in this context to a maximum period of 6 months.

Luteinizing Hormone-Releasing Hormone Agonist (LHRH Agonist)
LHRH analogues are effective in severe refractory cases of mastalgia but should not be used routinely or for prolonged periods. They act by inducing complete ovarian inhibition, resulting in low blood levels of estradiol or progesterone and prolactin.

Nonhormonal Treatment

Bromocriptine
Bromocriptine acts as a dopaminergic agonist on the hypothalamic-pituitary axis. It has demonstrated itself as effective in cyclical mastalgia but is not as effective as danazol.  Severe side effects have been noted with bromocriptine, hence, we do not recommend its use in treating mastalgia.

In summary, it is our experience that the majority of women can be dealt with by reassurance alone. Most of the others can be controlled with a short course of GLA, and it is only in the minority of patients that treatment regimens using drugs like danazol or LHRH agonists are necessary. It is our view that surgery has no place in the management of breast pain, and although anecdotal reports of women undergoing subcutaneous mastectomy for intractable mastalgia have emerged in the past, it is not a mode of practice that we endorse.

 

A.D. Purushotham, P. Britton and L. Bobrow
A prospective study of benign breast disease and the risk of breast cancer. JAMA 2002

References