Clinical Review - Benign breast disease

Contributed by Professor Kefah Mokbel, lead breast surgeon, The Princess Grace Hospital, and honorary consultant breast surgeon, St George's Hospital.

Ultrasound scan showing a simple cyst in the breast (Author images)
Ultrasound scan showing a simple cyst in the breast (Author images)

Section 1: Epidemiology and aetiology
The breasts are composed of several cell and tissue types, which can be broadly classified as either epithelial or stromal. These components are dynamic and hormone responsive.

Symptoms and signs relating to the breast can be considered to be either physiological or pathological. However, distinguishing between these can be challenging in general practice. In addition, breast conditions are frequently associated with significant anxiety. However, approximately 60% of patients referred for specialist evaluation are diagnosed with physiological or benign breast disease1 and almost half of these cases could be managed in the community.2

Classification
Mastalgia
Pain is the most common breast symptom reported in general practice. Many women experience some degree of premenstrual discomfort in the breast. Pain is rarely the sole presenting feature of cancer and usually does not necessitate further investigation.

Nodularity
The texture of breast tissue is seldom uniform and generalised thickening, often referred to as nodularity, is common. The differing density and unequal distribution of parenchyma in the breast is frequently associated with nodularity in the upper outer quadrants, which can feel quite discrete within the axillary tails. Focal nodularity is also a common finding in women taking oral contraceptives or HRT.

Cystic disease
Cysts are relatively common breast lumps. Approximately 7% of all women will encounter a palpable cyst in their lifetime.3 Although these lesions are non-proliferative, they can vary considerably in size and cause anxiety. Their presence can also affect the interpretation of clinical examination findings and diagnostic imaging. Cysts can be single or multiple, unilateral or bilateral and are frequently responsive to hormonal fluctuations.

Fibroadenoma
The majority of palpable solid breast lumps in young women are benign proliferative lesions called fibroadenomas. Although their precise aetiology has yet to be determined, fibroadenomas are known to be hormone responsive, are stimulated by estrogen, progesterone and lactation, and frequently regress after the menopause.4

Nipple discharge
Women presenting with nipple discharge account for 5% of all new referrals to specialist breast clinics. The discharge is physiological or hormone-related in many of these cases.

Inflammatory conditions
Inflammation of the breast (mastitis) is either lactational or non-lactational. The former is associated with ductal engorgement and floral entry through abrasions around the nipple secondary to breastfeeding.

Appropriate antibiotics are usually sufficient to treat Gram-positive bacteria (streptococci/staphylococci) and women should be encouraged to continue expressing milk from the affected side. Non-lactational mastitis occurs more frequently in smokers, particularly in the context of duct ectasia. Skin flora enter the breast in a retro-grade manner, resulting in periareolar mastitis and retro-areolar microabscess formation.

Section 2: Making the diagnosis
Mastalgia

For mastalgia, diagnostic imaging can be reserved for those patients who fall within current screening guidelines. Digital mammography is indicated in all women presenting with mastalgia aged ?40 years, or in younger women if they have an increased risk of breast cancer.

The differential diagnosis includes musculoskeletal, cardiac and radicular pain. Pain charts including a linear visual analogue scale are helpful.

Nodularity
During clinical examination, localised tenderness may be elicited within areas of focal nodularity.

The risk of pathology is significantly lower in younger women (less than 35 years and in those with symmetrical findings such cases it is appropriate to reassure re-examine three months preferably at a different time the woman's menstrual cycle.

Persistent, progressive or asymmetrical changes, particularly in older women or those with a family history, warrant referral. In the specialist setting, targeted ultrasonography is particularly informative in such cases, with the addition of mammography for women aged >35 years.

Fine needle aspiration cytology (FNAC) or core biopsy can be undertaken concurrently in cases where the imaging is equivocal or discordant.

Cystic disease
Most patients present with a lump, and/or pain. Following diagnostic confirmation with ultrasonography, symptomatic cysts can be treated with fine needle aspiration (FNA).

The aspirated fluid is not routinely sent for cytological evaluation, unless it is blood-stained or the cyst is complex. The solid component of complex cysts should also be subjected to core biopsy to exclude papillary and malignant cystic lesions.

Fibroadenoma
Fibroadenoma may be difficult to diagnose and patients may be referred for specialist evaluation. Ultrasonography is sufficient to provide reassurance. Simple fibroadenomas appear as solid hypoechoic masses, typically round/oval, with smooth, partially lobulated margins.


Calcified fibroadenoma

Mammography is undertaken in women aged ≥35 years and may demonstrate calcification (see image above). FNAC and/or percutaneous core biopsy are carried out to confirm the diagnosis. Giant fibroadenomas (>5cm) are more common in pregnant or lactating women.5 In such cases, it is essential to differentiate fibroadenomas from phyllodes tumours.

Nipple discharge
Nipple discharge is typically bilateral, low volume, white/yellow in colour and associated with nipple stimulation. Patients can be reassured and asked to return should there be any changes. In the absence of a recent history of breastfeeding, women with persistent galactorrhoea require investigations, such as serum prolactin and TFTs, and referral.6

Women with a single duct pathological nipple discharge (PND) should undergo clinical examination, imaging and cytological analysis. In many cases, PND can be attributed to benign breast disease, in particular, mammary duct ectasia or intraductal papilloma. However, surgical excision of the discharging duct is usually required to confirm diagnosis and relieve symptoms. Mammary ductoscopy has been introduced for the evaluation and treatment of PND.7

Inflammatory conditions
Ultrasound-guided aspiration, with samples sent for microbiological analysis, enables adequate drainage and anti-biotic prescription.

Section 3: Managing benign breast conditions
Mastalgia

Most women can be reassured because pain often resolves within a few months. Practical measures such as a well-fitted bra, weight reduction, regular exercise and reduced caffeine intake, should be recommended. Nutritional supplements that modulate the activity of endogenous estrogens may provide a modest benefit. These include flaxseed, a source of omega-3 fatty acids and lignan precursors.

At the other end of the spectrum, mastalgia can be persistent and severe. For this minority of patients, simple analgesia can be supplemented with targeted drugs.

The partial estrogen receptor agonist tamoxifen can be prescribed at low doses (5-10mg) for three to six months and has a more favourable side-effect profile in comparison to other agents such as danazol or bromocriptine. Cabergoline has been found to have comparable efficacy to bromocriptine, with fewer adverse effects.8

A recent RCT found lisuride maleate and topical NSAIDs to be effective for cyclical mastalgia, in comparison to evening primrose oil (EPO).9

Nodularity
Most patients can be reassured if the results of their investigations show no evidence of malignancy.

Cystic breast disease
Following the FNA of a simple cyst, the majority of patients can be discharged, although recurrence is a possibility. It is thought that women with gross cystic breast disease are at increased risk of breast cancer; however, the epidemiological evidence remains insufficient.10,11

Complex cases can be managed within the community, although patients should be referred to a breast specialist for baseline evaluation and to develop a management plan.

Fibroadenoma
Women with simple fibro-adenomas should be reassured that these lesions are not cancerous and malignant transformation is exceptional, with an incidence of 0.002%.12 Surgical excision should be reserved for uncertain diagnosis, large lesions (>3cm) or those which are increasing in size.5 Surgical excision is usually performed through an aesthetically placed periareolar incision. Vacuum-assisted removal under local anaesthesia through a 3mm incision is a valid alternative. For most cases, particularly young women with small lesions, reassurance is all that is necessary. Specialist follow-up is not required.


Fibroadenoma before vacuum core biopsy needle (top); the lesion resolved after the procedure (bottom)

Nipple discharge
Surgical excision of the discharging duct, with microdochectomy or total duct excision, is usually required to establish the histological diagnosis and relieve symptoms. For some women (approximately 5%), PND is associated with breast carcinoma, which requires management by a multidisciplinary team.

Inflammatory disease
Amoxicillin-clavulanate is recommended for acute mastitis. Specialist referral will be required where there are breast abscesses.

Ultrasound-guided aspiration, with samples sent for microbiological analysis, and antibiotic prescription are required. These patients can present similarly to those with inflammatory breast cancer, so once infection is treated, specialist assessment will be required, especially in non-lactating women aged ≥40 years.

CRITERIA FOR SPECIALIST REFERRAL
1. Unilateral non-cyclical mastalgia in a woman aged 35 years or over
2. The presence of a discrete breast lump
3. Persistent non-cyclical asymmetric nodularity
4. Spontaneous single duct nipple discharge
5. Blood-stained pathological nipple discharge
6. Mastitis not responding to antibiotic therapy
7. Breast abscess
8. Inflammation or ulceration of the nipple areola complex
9. Retraction or inversion of the nipple
10. Retraction or tethering of the skin overlying the breast

Section 4: Prognosis
A variety of physiological conditions and benign breast diseases have been discussed here. Despite their diversity, there exists an overarching common theme. Patients with breast conditions are, for the most part, seeking reassurance. Most benign breast conditions are estrogen dependent and therefore tend to regress or resolve after the menopause or cessation of HRT. This particularly applies to cysts, nodularity, hormone-related nipple discharge and fibrocystic change.

In relation to fibroadenomas, approximately 50% remain stable, 25% decrease or resolve and 25% increase in size over time. Fibroadenomata and papillomata rarely recur following complete surgical excision.

Cancer risk
Furthermore, after diagnosis and management, patients often enquire if their risk of developing breast cancer is increased. This information is also essential to the clinician, in order to determine the nature and frequency of any subsequent follow-up or surveillance.

Benign breast disease can be classified into conditions that are non-proliferative, proliferative or proliferative with atypia. Non-proliferative lesions and proliferative lesions without atypia are not associated with an increased risk of breast cancer, although vigilance is appropriate because they can affect the interpretation of subsequent examination findings and diagnostic imaging.

Atypical hyperplasia is associated with an increased risk of breast cancer, particularly in those with a significant family history, so specialist guidance should be sought to determine the appropriate surveillance.

Section 5: Case study
A 23-year-old woman presented to her GP with a two-week history of a painful lump in the left breast. She was nulliparous and did not take the oral contraceptive pill. There was no family history of breast cancer.

Specialist referral
The GP examined the patient and confirmed the presence of a 15mm smooth well-defined solid mass lesion in the upper inner quadrant of the left breast.

The GP reassured her and referred her to the specialist breast clinic. The breast surgeon confirmed the clinical finding reported by the GP, arranged an ultrasound scan and performed a clinical FNAC. The ultrasound scan showed a 15mm well-defined hypoechoic solid mass lesion in the upper inner quadrant of the left breast. FNAC demonstrated benign epithelial cells consistent with fibroadenoma. The patient was reassured and given the option of conservative treatment or removal.

She requested removal due to anxiety and localised discomfort. The surgeon offered her two options - vacuum-assisted removal under ultrasound guidance or open excision through a periareolar incision. She opted for the former and the procedure was performed through a 3mm incision under local anaesthesia in the clinic setting. The final histology confirmed a benign fibroadenoma. The images above show the lesion before and after the procedure.

Section 6: Evidence base
The evidence regarding the natural history and management of benign breast disease has been derived primarily from descriptive pathological, observational and retrospective studies. RCTs have rarely been used in this context.

The treatment of mastalgia, for example, has been subjected to such trials, whereas the management of a common condition like fibroadenoma has not been subjected to RCTs.

Clinical trials

  • 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.

These authors conducted a meta-analysis of all mastalgia trials published in the English language. The study was restricted to RCTs comparing bromo-criptine, danazol, EPO and tamoxifen with placebo. The analysis showed that EPO offered no advantage over placebo in pain relief. Bromocriptine and danazol produced a significant benefit, with a mean pain score difference. Low-dose tamoxifen (5mg daily) was effective and had fewer side-effects.

This study demonstrated that cabergoline (0.5mg weekly) is as effective as bromocriptine for the treatment of cyclic mastalgia, but has minimal side-effects compared to bromocriptine.

Guidelines

Key text

  • Hughes LE, Mansel RE, Webster DJT. Benign Disorders and Diseases of the Breast (third edition). Philadelphia, WB Saunders, 2009.

Online

This is a useful overview of benign breast disease.

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

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.
  • Make a poster for your clinical rooms, defining the clinical pathways and referral criteria for breast diseases.
  • Attend a breast clinic at your local hospital to gain more experience in managing breast conditions.
  • Review your practice’s referrals to secondary care over the past year and discuss each case at a clinical meeting.

 

References
1. Laver RC, Reed MW, Harrison BJ et al. Ann R Coll Surg Engl 1999; 81(4): 242-7.

2. Morrow M. Am Fam Physician 2000; 61: 2371-8, 2385.

3. Tohno E, Cosgrove DO, Sloane JP. Ultrasound Diagnosis of Breast Diseases. London, Churchill Livingstone, 1994.

4. Hughes LE, Mansel RE, Webster DJT. Lancet 1987; 11: 1316-19.

5. Greenberg R, Skornick Y, Kaplan O. J Gen Intern Med 1998; 13(9): 640-5.

6. Vaidyanathan L, Barnard K, Elnicki M. Cleve Clin J Med 2002; 69(5): 425-32.

7. Mokbel K, Escobar PF, Matsunaga T. Eur J Sur Oncol 2005, 31: 3-8.

8. Aydin Y, Atis A, Kaleli S et al. Eur J Obstet Gynecol Reprod Biol 2010; 150(2): 203-6.

9. Qureshi S, Sultan N. Surgeon 2005; 3(1): 7-10.

10. Naldoni C, Constantini M, Dogliotti L. Cancer Res 1992; 52: 1791-5.

11. Mannello F, Tonti G, Papa S. Breast Cancer Res Treat 2006; 97: 115-29.

12. Deschenes L, Jacob S, Fobia J et al. Can J Surg 1985; 28: 372-3.

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