Ductal Carcinoma in Situ of the Breast

Ductal carcinoma in situ (DCIS) is a clonal proliferation of malignant epithelial cells confined to the mammary duct and lobular system, with an intact myoepithelial layer and basement membrane. It is a non-obligate precursor of invasive breast carcinoma and has no metastatic potential until invasion occurs.

Most cases are found by screening mammography, where DCIS makes up roughly 20% to 25% of screen detected cancers. In unscreened populations it is uncommon and presents as a palpable mass, nipple discharge or Paget disease of the nipple.

Median age at diagnosis is in the early to mid 50s. Associations match invasive breast cancer: age, first degree family history, pathogenic variants in BRCA1, BRCA2 and PALB2, nulliparity or late first birth, prolonged oestrogen exposure, combined hormone replacement therapy, high breast density and prior atypical hyperplasia.

Pathophysiology. DCIS arises in the terminal duct lobular unit through accumulated genomic change that parallels invasive disease of the same grade. Low grade lesions are mostly oestrogen receptor positive and HER2 negative. High grade lesions often overexpress HER2 and are more often receptor negative.

Grading. Nuclear grade (low, intermediate, high) and comedo type necrosis define risk. High grade lesions are larger and more extensive, and usually show fine linear branching or pleomorphic calcification.

Natural history. Low grade lesions initially misread as benign and left untreated progressed to invasive cancer in roughly 14% to 50% over 10 to 40 years. Progression is therefore common but not inevitable, which drives the debate about overtreatment of low risk lesions.

Outcome. After treatment, breast cancer specific mortality is about 3% at 20 years. After breast conserving surgery alone, ipsilateral recurrence is about 25% to 30% at 10 years, roughly half of it invasive. Whole breast radiotherapy cuts this by about half.

Microinvasion. Invasion of 1 mm or less through the basement membrane is microinvasion. It carries a small risk of nodal metastasis (under 10%), and axillary staging is considered when the focus is multiple or the lesion is high grade.

• Most patients are asymptomatic. The lesion appears on mammography as clustered microcalcification (about 70% to 80% of mammographic cases), or less often as a mass, distortion or asymmetric density.
• Symptomatic presentations are unilateral single duct nipple discharge (serous or bloodstained), Paget disease of the nipple, or a palpable lump. A lump suggests larger extent or coexisting invasion.
• Examination is usually normal. Palpable axillary nodes indicate invasive disease until proved otherwise.

• Mammography: bilateral two view with magnification views of calcification. Fine linear branching and fine pleomorphic calcification are the highest risk forms. Measure extent in two planes.
• Ultrasound: for any mass, for discharge, and for the axilla.
• Biopsy: vacuum assisted stereotactic core biopsy (9 to 11 gauge) with a specimen radiograph to confirm that calcified cores were retrieved, and a marker clip placed. Cytology is inadequate.
• Histology report: nuclear grade, necrosis, architecture, extent, oestrogen and progesterone receptor status. Myoepithelial markers (p63, calponin, smooth muscle myosin) are used when invasion is in doubt. HER2 testing is not routine.
• Upstaging: about 20% to 25% of core biopsy DCIS contains invasive carcinoma at excision. The rate is higher with a palpable mass, high grade, size over 2 cm or a mammographic mass.
• MRI is not routine. It is useful for discordant size, dense breasts, young age or planned oncoplastic surgery.
• Distant staging is not indicated for pure DCIS.
• Axilla: nodal metastasis occurs in 1% to 2% of apparent pure DCIS, mostly from missed invasion. Sentinel node biopsy is omitted with breast conservation. It is done with mastectomy, because a later finding of invasion would make it unreliable, or when invasion is suspected.

Differential diagnosis.

• Atypical ductal hyperplasia (limited extent, under 2 mm or fewer than two duct spaces)
• Lobular carcinoma in situ (florid and pleomorphic types)
• Invasive carcinoma with an in situ component
• Benign calcification (columnar cell change, sclerosing adenosis, fat necrosis, secretory calcification)
• Intraduct papilloma and encapsulated papillary carcinoma
• Duct ectasia

The aim is to eradicate local disease and prevent invasive recurrence.

Surgery.

• Breast conserving surgery with radiologically and histologically clear margins. A margin of at least 2 mm is usual practice. Involved margins need re-excision.
• Mastectomy for extensive or multicentric disease where clear margins cannot be achieved with acceptable shape, persistent positive margins, contraindication to radiotherapy, or patient choice. Skin sparing or nipple sparing mastectomy with immediate reconstruction is an option. Local recurrence after mastectomy is under 2%.
• Sentinel node biopsy is done with mastectomy. It is not done with breast conservation unless invasion is suspected.

Radiotherapy after breast conserving surgery.

• Whole breast 40 Gy in 15 fractions over 3 weeks. A tumour bed boost of about 10 to 16 Gy is added for age under 50, high grade, close margins or large extent.
• Radiotherapy can be omitted after discussion for low or intermediate grade lesions under 2.5 cm with margins over 3 mm in older screen detected patients. The recurrence rate is higher without it.

Endocrine therapy for oestrogen receptor positive DCIS after conservation lowers breast cancer events (ipsilateral and contralateral) by roughly 30%.

• 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.
• Endocrine therapy after mastectomy lowers only the risk of a new cancer in either breast, and is optional.

Chemotherapy and HER2-directed therapy have no role.

Monitoring. Bilateral mammography annually, the first 6 to 12 months after radiotherapy, then lifelong. Clinical examination every 6 to 12 months for 5 years. MRI is added for pathogenic variant carriers.

Referral and escalation.

• All patients go to a multidisciplinary breast team before definitive surgery.
• Urgent re-referral for a new mass, skin or nipple change, or bloodstained discharge after treatment.
• Genetic counselling for age under 45, bilateral disease or a significant family history.

Special groups.

• Pregnancy: surgery is possible in any trimester. Defer radiotherapy and endocrine therapy until after delivery.
• Pathogenic variants (BRCA1, BRCA2, PALB2, TP53): consider bilateral mastectomy. Avoid radiotherapy where possible in TP53 carriers.
• Age under 40: higher recurrence. Use wide margins, a boost and endocrine therapy.
• Older adults with limited life expectancy: endocrine therapy alone or observation after discussion.
• Men: mastectomy is usual, with tamoxifen 20 mg once daily for 5 years if receptor positive.