Mucinous Breast Carcinoma

Mucinous (colloid) carcinoma is an invasive breast cancer in which clusters of tumour cells float in pools of extracellular mucin. The pure type has mucin in over 90% of the tumour, and the mixed type has 10% to 90% mucin with an invasive ductal component.

It accounts for 1% to 4% of breast cancers, with the pure type about 2%. It occurs mainly in postmenopausal women, with a median age in the 60s to 70s, and grows slowly.

There is no distinct hereditary or environmental association. Risk factors are those of luminal breast cancer.

Pathophysiology. Tumour cells secrete MUC2-rich mucin, which forms a barrier around cell clusters. A hypocellular type (type A) and a hypercellular type (type B, with neuroendocrine differentiation and synaptophysin or chromogranin positivity) are described.

Receptor profile. ER is positive in over 90%, PR in about 80% and HER2 is negative in over 95%. Grade is low to intermediate with low proliferation, a luminal A-like phenotype.

Behaviour. Pure tumours involve axillary nodes in about 2% to 14%, and ten year survival is over 90%. Mixed tumours behave like invasive ductal cancer, with higher nodal rates and relapse. Late recurrence beyond 10 years is reported.

• Soft, well circumscribed, mobile, painless mass, usually 2 to 4 cm, slow growing, with a gelatinous cut surface.
• Skin and nipple involvement are uncommon.
• Axillary nodes are rarely palpable.

• Mammography: well circumscribed lobulated or microlobulated mass, calcification uncommon. Ultrasound: iso- or hypoechoic, sometimes complex, with posterior enhancement. MRI: markedly bright on T2-weighted sequences.
• Core biopsy shows tumour clusters in abundant mucin. Hypocellular samples can understate the invasive component, so excision confirms the pure or mixed type. Report ER, PR, HER2 and proliferation.
• Metastasis from the gastrointestinal tract, ovary or pancreas is excluded when clinically suspected. Breast origin is supported by GATA3 and ER positivity and CDX2 and CK20 negativity.
• Systemic staging only for node positive, large or symptomatic disease. 21-gene recurrence score for node positive disease (pure tumours usually score low).

Differential diagnosis.

• Mucocele like lesion (benign, with possible associated DCIS)
• Fibroadenoma and simple or complex cyst
• Mixed mucinous and ductal carcinoma
• Metastatic mucinous adenocarcinoma
• Invasive micropapillary carcinoma
• Cystic papillary carcinoma

Surgery. Breast conservation with clear margins or mastectomy. Sentinel node biopsy is usual, though low nodal risk in small pure tumours makes it a point of discussion.

Radiotherapy. After conservation, whole breast 40 Gy in 15 fractions, with a boost of about 10 to 16 Gy for higher risk cases. Post-mastectomy radiotherapy for T3 to T4 disease or 4 or more positive nodes.

Endocrine therapy for ER-positive disease:

• Tamoxifen: 20 mg orally once daily for 5 years (up to 10 years in selected higher risk women); maximum 20 mg daily; monitoring: ask about abnormal vaginal bleeding at each visit, thromboembolic symptoms, annual gynaecological review; adjustment: no renal adjustment, avoid strong CYP2D6 inhibitors (paroxetine, fluoxetine, bupropion), avoid in severe hepatic impairment and pregnancy, caution with prior venous thromboembolism.
• Anastrozole (postmenopausal women): 1 mg orally once daily for 5 years (letrozole 2.5 mg or exemestane 25 mg once daily are equivalent options); maximum 1 mg, 2.5 mg and 25 mg daily respectively; monitoring: bone mineral density at baseline then every 1 to 2 years, calcium and vitamin D, lipids, arthralgia; adjustment: none in mild to moderate renal or hepatic impairment, letrozole 2.5 mg every other day in severe hepatic impairment.

Chemotherapy. Not needed for pure, node negative tumours. For mixed tumours and node positive disease, decisions follow ductal cancer principles and the recurrence score.

Monitoring. Clinical review every 6 to 12 months and annual mammography. Maintain surveillance beyond 10 years because of late recurrence.

Referral and escalation.

• Multidisciplinary breast review before definitive surgery.
• Urgent review of any new mass, skin change or bone pain during follow up.

Special groups.

• Older adults with limited life expectancy: surgery with endocrine therapy, and omission of radiotherapy in small, node negative tumours.
• Pregnancy: defer endocrine therapy and radiotherapy until after delivery.