Tubular Breast Carcinoma

Tubular carcinoma is a well differentiated invasive breast cancer in which over 90% of the tumour forms open, angulated tubules lined by a single layer of epithelial cells with apical snouts, within a desmoplastic stroma. It has an excellent prognosis.

It makes up 1% to 2% of breast cancers in symptomatic series and a higher proportion in screened populations (up to about 4%). Median age is around 50 to 60 and tumours are usually under 2 cm.

Associations are screening detected small stellate lesions and a coexisting lobular neoplasia or flat epithelial atypia. Risk factors are those of luminal breast cancer.

Pathophysiology. Almost all tumours are ER positive, most are PR positive, and HER2 is negative. Proliferation is low, with few genomic alterations (often gain of 1q and loss of 16q), so it sits at the low grade end of the luminal spectrum with flat epithelial atypia, atypical ductal hyperplasia and lobular neoplasia as likely precursors.

Mixed tumours. Tumours with 50% to 90% tubular architecture behave like low grade ductal carcinoma, and mixed tumours with a higher grade component follow that component.

Behaviour. Axillary node involvement is about 5% to 10%, usually 1 to 3 nodes. Ten year breast cancer survival is about 95% to 100%. Late contralateral breast cancer is more frequent than local relapse.

• Mostly asymptomatic, found on screening as a small stellate or spiculated mass or architectural distortion.
• Palpable lesions are small, firm and irregular, often without skin changes.

• Mammography: small spiculated mass, sometimes indistinguishable from radial scar. Ultrasound: irregular hypoechoic mass with posterior shadowing. MRI shows an irregular enhancing mass.
• Core biopsy (at least 3 cores, preferably vacuum assisted): open tubules with angulation, apical snouts and no myoepithelial layer (p63, calponin and smooth muscle myosin negative around tubules). Elastosis and desmoplasia are present. Excision is advised when core biopsy cannot separate tubular carcinoma from radial scar.
• ER, PR and HER2 testing. Axillary ultrasound. Staging only for node positive or symptomatic disease.

Differential diagnosis.

• Radial scar and complex sclerosing lesion (myoepithelial layer present)
• Microglandular adenosis
• Sclerosing adenosis
• Low grade adenosquamous carcinoma
• Tubulolobular and invasive cribriform carcinoma
• Well differentiated invasive ductal carcinoma

Surgery. Wide local excision with clear margins, or mastectomy for extensive disease. Sentinel node biopsy is performed, because 5% to 10% are node positive.

Radiotherapy. After conservation, whole breast 40 Gy in 15 fractions. Radiotherapy can be omitted after discussion in women aged 65 or over with ER-positive, node negative tumours under 2 cm who take endocrine therapy for 5 years, because absolute local recurrence is low.

Endocrine therapy:

• Tamoxifen: 20 mg orally once daily for 5 years; 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 in pure tubular carcinoma, even with 1 to 3 positive nodes. Use the recurrence score for mixed or node positive disease.

Monitoring. Annual mammography with clinical review every 6 to 12 months. Contralateral surveillance is important.

Referral and escalation.

• Breast multidisciplinary review when core biopsy diagnosis of radial scar or tubular carcinoma is uncertain.
• Genetic counselling when there is a significant family history.

Special groups.

• Older adults: surgery with endocrine therapy alone is reasonable, with omission of radiotherapy in women aged 65 or over with small oestrogen receptor positive node negative tumours.
• Pregnancy: surgery in any trimester, with endocrine therapy deferred.