Clinical Review: Benign breast disease

Benign breast diseases constitute a heterogeneous group of lesions including developmental abnormalities, inflammatory lesions, epithelial and stromal proliferations, and neoplasms.

Mammogram of fibroadenoma (SPL)
Mammogram of fibroadenoma (SPL)

Section 1: Epidemiology and aetiology

About 90% of patients referred to breast units are diagnosed with a benign condition. As well as excluding breast cancer and providing reassurance, patients expect a tailored approach to their benign condition.

Fibroadenomas
Fibroadenomas arise from breast lobules and are composed of fibrous and epithelial tissue.

They are highly mobile, because of the encapsulation and pliability of young breast tissue.

Clinically, fibroadenomas are difficult to differentiate from phyllodes tumours, which is a distinct pathology. The latter are sarcomas which rapidly enlarge and have variable degrees of malignant potential. They are larger than fibroadenomas and tend to occur in an older age group (15-20 years later).

Mastalgia
Mastalgia, which is also known as mastodynia or mammalgia, refers to breast pain. Causes of mastalgia should be differentiated (see table 1).

Table 1: Differentiating mastalgia
Referred chest wall pain
  • Musculoskeletal
  • Costochondritis (Tietze’s syndrome)
  • Fibromyalgia rheumatica    
True mastalgia
  • Idiopathic
  • Exogenous hormone
  • Latent hyperprolactinaemia    
Non-breast cause
  • Cervical spondylosis
  • Lung disease
  • Shingles

True mastalgia is more common in women taking hormonal contraceptives (oral, implant, injection or intrauterine) or menopausal HRT.

Combined estrogen-progestogen HRT preparations are known to cause more severe mastalgia than estrogen-only preparations.1

Recent evidence suggests that latent stress-induced hyperprolactinaemia can cause mastalgia. Referred breast pain from the chest wall is often musculoskeletal or neurological in origin.

Cysts
Cysts are fluid-filled, distended, involuted lobules. They are more common in women from the age of 35 years up to the menopause.

In fibrocystic disease, the overgrowth of glandular and connective tissue tends to block ducts, causing lobules to widen and fill with fluid.

Gynaecomastia
Gynaecomastia is hyperplasia of the male breast stromal and ductal tissue. It is usually caused by a relative increase in the estrogen to androgens ratio in the circulation or breast tissue.

The most common cause is secondary to drugs. In older patients, it involves cardiovascular and prostate drugs, and in younger patients, cannabis, anabolic steroids, anti-ulcer drugs and antidepressants.
Gynaecomastia can also be physiological and present spontaneously in a trimodal age pattern; neonates, pubertal and senescence. These cases are usually self-limiting.

Other common pathological causes include undiagnosed hyperprolactinaemia, liver failure, alcohol excess, obesity and malignancy (testes and lung).

Mastitis
Lactational mastitis can occur in 5% of puerperal women. Staphylococcus aureus enters the duct through the nipple skin break and thrives in that culture media.2 Inadequate ductal drainage leads to colonisation, infection and progression to an abscess.

Periductal mastitis, a common non-lactational infection, is associated with younger women and smoking. Smoking leads to accumulation of toxic metabolites and overgrowth of aerobic and anaerobic Gram- negative bacteria,3 leading to ductal inflammation and abscess.

Nipple discharge
Ductal causes include intraduct papilloma, a stalk-like epithelial lesion that grows in large ducts within 5cm of the nipple. It is the most common cause of unilateral, spontaneous, single duct bloody nipple discharge.

Duct ectasia is another condition involving age-related dilation and shortening of the terminal ducts.

It presents as a creamy or brown serous discharge.

Galactorrhoea is a physiological cause, presenting as bilateral, white, milky, multiduct discharge. This can be caused by latent hyperprolactinaemia, drugs or a hypersecreting pituitary tumour, or may be idiopathic.

Fat necrosis
Fat necrosis occurs after breast trauma and may present with a palpable lump.

Section 2: Making the diagnosis

Symptomatic patients are referred to the breast clinic for triple assessment (history and examination, ultrasound and/or bilateral mammography and biopsy).

Lumps
Fibroadenomas appear as a well-defined, smooth, oval-shaped lump, distinctly mobile and easily identified on ultrasound.

Young patients (less than 25 years) with clearly benign clinical and imaging findings are usually spared a core biopsy. Older patients have to rule out occult malignancy phyllodes tumour.

Cysts are common in perimenopausal women, although they can occur at any age in women on hormonal contraceptives or HRT.

Patients present with a painful lump, which grows rapidly in the luteal phase of their cycle and tends to shrink on menstruation. Cysts are easily identified on ultrasound.

Gynaecomastia presents in a male patient with an enlarging, painful breast lump. Detailed drug history and use of recreational or anabolic steroids should be elicited, as well as weekly alcohol intake and recent weight gain.

Examination reveals a 2-4cm round, tender, soft ‘disc’ of breast tissue behind the nipple. General, abdominal and scrotal examination should be performed to identify obesity, liver failure and testicular cancer.

Ultrasonography may be used to confirm gynaecomastia and exclude male breast cancer. Some men tend to decline mammography. Routine blood tests should include serum prolactin, total testosterone, LFTs, alpha-fetoprotein and beta-hCG.

Fat necrosis presents as a soft, indistinct lump that develops a few weeks after a traumatic incident, and often in older women with fatty breasts. On imaging, some are difficult to distinguish from breast cancer and a core biopsy is often indicated.

Mastalgia
Differentiate between breast and non-breast causes. The history should include the timing, character and location of the pain, gynaecological history, hormonal contraceptive or HRT use and any previous breast surgery.

True mastalgia is described as a sharp pain occurring mainly in the week before menstruation, followed by relief on menstruation. The pain could be intermittent or constant.

It is localised to the upper and central breast. Serum prolactin can be checked in premenopausal patients.

For chest wall mastalgia, patients are usually postmenopausal and not using HRT. The pain is unilateral, described as an ache, localised to the medial and lateral breast and brought on by shoulder activity.

In addition to routine examination, ask the patient to lie on each side in turn. This lets the breast fall away, allowing the medial and lateral chest wall to be palpated.

Tenderness in the rib prominence or muscle usually indicates chest wall pain. Paraesthesia usually indicates a neurological cause. The only imaging required by most patients with mastalgia but no discrete palpable finding is a screening mammogram.

Nipple discharge
Differentiate between a physiological and a ductal cause. History- taking should include age, discharge features, medical and drug history (antipsychotics) and breastfeeding.

Discharge fluid should be sent for cytological examination, to identify blood or atypical/malignant cells. Imaging should aim to identify intraduct papillomas, duct ectasia or underlying malignancy. If a physiological cause is suggested in bilateral white discharges, a serum prolactin test is warranted.

Infection
Lactational mastitis presents as a patch of painful red skin and oedematous swelling. It may rapidly progress to a fluctuant abscess.

Deep-seated abscesses are difficult to identify on ultrasound.

Periductal mastitis presents as a painful lump that commonly occurs at the edge of the areola. With continued smoking, this progresses to abscess, then ruptures to leave a sinus.

Section 3: Managing the condition

For small biopsy-confirmed fibroadenomas, no further follow-up is required.

Surgical excision is indicated for fibroadenomas that are rapidly enlarging, larger than 4cm, if the core biopsy is inconclusive, or on patient request.

This can be achieved through vacuum-assisted 8G mammotomy under local anaesthesia (for small lesions) or open excision under general anaesthesia.

Mastalgia
For both chest wall and true mastalgia, the main treatment is reassurance.4 For chest wall related pain, advice on lifestyle changes, such as more regular gentle exercise, oral paracetamol and topical NSAID gels, can provide relief.

In persistent cases, an injection of steroids and long-acting local anaesthetic can be administered.5

For true mastalgia, a sports bra can reduce pain, especially when sleeping.

Daily gamma-linoleic acid, in the form of evening primrose oil and starflower oil, is no longer indicated since a 2005 RCT showed it was equally effective as placebo.6

Agnus castus, a fruit extract, has prolactin-suppressing and estrogen-reducing properties, and RCTs have shown it to be superior to controls.7

There is no evidence that caffeine abstinence is effective.

Stopping hormonal contraceptives for a few months then recommencing (using barrier methods in the meantime) could be tried. This approach is purely anecdotal and there are no formal studies to confirm the practice.

Tamoxifen (10-20mg) has been shown in meta-analysis to be superior (and to have fewer side-effects) when compared with bromocriptine and danazol.8

Gynaecomastia
For idiopathic gynaecomastia, management includes reassurance that the condition is self-limiting. In severely painful cases, a six-week trial of daily 10mg tamoxifen is indicated, but is contraindicated in those with previous thromboembolic disease.9

Causative medication can be continued in mild cases, but should be stopped or changed in painful or worsening gynaecomastia.

Suitable alternative cardiovascular medications include candesartan, bisoprolol and metoprolol.
Surgical excision can be offered via open excision or liposuction, although  strict criteria on BMI must be met for NHS funding.

For those with abnormal serum hormone profiles, an endocrinology referral is indicated.

Cysts
For cysts, no further action is necessary. Needle aspiration is reserved for large, painful cysts or if there is doubt as to whether the lesion is solid or contains fluid. Aspirated cyst fluid is only cytologically examined if it appears bloody.

Needle aspirations tend to lead to atypical cyst appearance, which may in turn lead to unnecessary core biopsies in future.

For fat necrosis, no further follow-up is required if confirmed benign.

Nipple discharge
For nipple discharge cases where an intraduct papilloma is identified, open or vacuum excision is indicated to confirm benignity.

In patients with red flag features, which include unilateral, spontaneous, bloody nipple discharge, or the presence of atypical or red blood cells on cytology, or of a ductal lesion on imaging, an open biopsy is required to exclude malignancy.

This procedure is usually a microdochectomy (removal of a single discharging duct) or a total duct excision (dividing all ducts, removing breast tissue up to 2cm below the nipple). The former is indicated in women of child-bearing age because it preserves the integrity of the remaining ducts.

These two procedures can be used in symptomatic control in women with troublesome, persistent discharge. Duct ectasia does not require any intervention.

Mastitis
For patients with lactational mastitis and abscesses, conservative management includes continued breastfeeding, by suckling or breast pump, to encourage ductal drainage.

Adult dose penicillin-based antibiotics are safe for lactating mothers and their babies.

Repeated needle aspirations under ultrasound guidance and local anaesthesia may help with resolution and obtain accurate microbiology. If the skin overlying the abscess looks thin or necrotic, incision and drainage under general anaesthesia is indicated.

For periductal mastitis, mild cases resolve with smoking cessation and antibiotics, which should include anaerobic cover (flucloxacillin and metronidazole). Repeated needle aspiration or incision and drainage may be required for abscesses.

Repeated infection despite smoking cessation and prophylactic antibiotics can be resolved by total duct excision or nipple excision. Mammography is imperative once the infection has resolved, to exclude malignancies.10

Section 4: Prognosis

Most breast conditions do not increase breast cancer risk, except for atypical ductal/lobular hyperplasia, atypical columnar cell change, multiple papilloma (papillomatosis), juvenile papillomatosis and lobular neoplasia. These patients require annual mammographic screening.11

Some early studies suggested a very small increase in breast cancer risk in patients with cysts, but
this was not considered to warrant earlier screening.12

A study carried out in Edinburgh showed that over a two-year period, fewer than 10% of common fibroadenomas increase in size, about one-third become smaller or completely disappear, and the remainder stay the same size. Fibroadenomas rarely undergo malignant transformation.13

There is no associated increased risk of male breast cancer in gynaecomastia. Mastalgia is not associated with increased breast cancer risk – on the contrary, one large study suggested that it was associated with a lower incidence of breast cancer.14

Section 5: Case study

A 45-year-old woman presented with a three-month history of a sharp, constant pain arising from the back of her left breast and radiating to her left nipple and arm.

This pain kept her awake at night and she was anxious that it might be caused by breast cancer.

There was no significant past medical or drug history. She had an IUD inserted four years previously for contraception. There was no family history of any cancer.

On examination, the patient was tender at the lateral aspect of her left breast. There was a palpable 2cm round, soft, tender, immobile lump at the upper inner quadrant (UIQ) of the breast, consistent with a cyst.

Examining the patient on her side showed that the tenderness arose from the breast, not the chest wall.

Left mammogram revealed a round halo consistent with a cyst at the UIQ of the breast. Ultrasound confirmed a 17mm x 16mm x 19mm cyst with numerous small cysts throughout both breasts. The glandular tissue within the tender lateral areas was particularly dense.

Before the end of the clinic, the patient was reassured and informed that she had a small cyst, which did not require needle aspiration because it was asymptomatic and would usually resolve spontaneously. She was also advised that mastalgia was not associated with increased breast cancer risk.

Although cysts do not transform into breast cancer, they are statistically associated with a very small increase in breast cancer risk. However, because this patient had no family history of breast cancer, her risk remained the same as the general population and early breast screening was not indicated.

The pain was severe, so she opted to have the IUD removed and to use barrier contraception instead. She started taking oral paracetamol as required.

At the three-month follow-up, the cyst had disappeared, but her left mastalgia was still severe and affecting her quality of life. Serum prolactin was normal.

She was started on 10mg tamoxifen for three months and counselled on hot flushes and the small increased risk of thromboembolic disease and uterine cancer. She was also asked to look out for intermenstrual bleeds.

On further three-month follow-up, her pain had resolved. She was asked to stop the tamoxifen and then discharged.

Section 6: Evidence base

Guidelines

  • Willett AM, Michell MJ, Lee MJ (eds). Association of Breast Surgeons: Best practice diagnostic guidelines for patients presenting with breast symptoms. London, DH, November 2010.

Online

Key text

  • Dixon JM. ABC of Breast Diseases (fourth edition). Chichester, Wiley-Blackwell, 2012.

Contributed by Mr Kelvin Chong, consultant oncoplastic breast surgeon, Spire Bushey Hospital and West Herts NHS Trust.

CPD IMPACT: EARN MORE CREDITS

These further action points may allow you to earn more credits by increasing the time spent and the impact achieved.

  • Review your local referral policy for patients with breast lumps.
  • Arrange a meeting with a local breast surgeon to discuss optimum management of women with breast conditions.
  • Have leaflets available for women with mastalgia, which include information about treatment recommendations.

Click here to reflect on this article and add notes to your CPD organiser on MIMS Learning

References

1. Crandall CJ, Aragaki AK, Cauley JA et al. Breast tenderness and breast cancer risk in the estrogen plus progestin and estrogen-alone women's health initiative clinical trials. Breast Cancer Res Treat 2012; 132(1): 275-85.
2. Dabbas N, Chand M, Pallett A et al. Have the organisms that cause breast abscess changed with time? Implications for appropriate antibiotic usage in primary and secondary care. Breast J 2010; 16(4): 412-15.
3. Schafer P, Furrer C, Mermillod B. An association of cigarette smoking with recurrent subareolar breast abscess. Int J Epidemiol 1988; 17(4): 810-13.
4. Barros AC, Mottola J, Ruiz CA et al. Reassurance in the treatment of mastalgia. Breast J 1999; 5(3): 162-5.
5. Iddon J, Dixon JM. Mastalgia. BMJ 2013; 347: f3288.
6. Goyal A, Mansel RE. A randomized multicenter study of gamolenic acid (Efamast) with and without antioxidant vitamins and minerals in the management of mastalgia. Breast J 2005; 11(1): 41-7.
7. Carmichael AR. Can vitex agnus castus be used for the treatment of mastalgia? What is the current evidence? Evid Based Complement Alternat Med 2008; 5(3): 247-50.
8. Srivastava A, Mansel RE, Arvind N et al. Evidence-based management of mastalgia: a meta-analysis of randomised trials. Breast 2007; 16(5): 503-12.
9. Khan HN, Blamey RW. Endocrine treatment of physiological gynaecomastia. BMJ 2003; 327(7410): 301-2.
10. Dixon JM. Breast infection. BMJ 2013; 347: f3291.
11. Buckley ES, Webster F, Hiller JE et al. A systematic review of surgical biopsy for LCIS found at core needle biopsy – do we have the answer yet? Eur J Surg Oncol 2014; 40(2): 168-75.
12. Bundred NJ, West RR, Dowd JO et al. Is there an increased risk of breast cancer in women who have had a breast cyst aspirated?
Br J Cancer 1991; 64(5): 953-5.
13. Dixon JM. ABC of Breast Diseases (fourth edition). Chichester, Wiley-Blackwell, 2012.
14. Khan SA, Apkarian AV. Mastalgia and breast cancer: a protective association? Cancer Detect Prev 2002; 26(3): 192-6.

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